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The Influence of Relative Brain Size on Cranial Morphology in a Mouse Model of Encephalization

ProQuest Dissertations and Theses, 2011
Dissertation
Author: Elisabeth Kathleen Nicholson Lopez
Abstract:
The lack of experimental models of brain expansion together with a dearth of information regarding fetal brain development detracts from a complete understanding of cranial integration and its relevance to the ontogenetic and interspecific patterning of the craniofacial morphology. To address this shortcoming, this study uses two datasets to examine the changes in cranial form associated with an increase in encephalization. First, mice expressing a stabilized form of β-catenin were used to isolate the effects of encephalization on the development of the basicranium and neurocranium. These transgenic mice have an increased number of neural precursors, which results in the development of an enlarged brain. Morphological differences between groups were predicted to ultimately result from variation in encephalization. Second, morphological data for fetal modern humans with normal and pathological conditions were analyzed. Like the mouse sample, the human sample was intraspecific. However, the degree of encephalization was not the only factor separating specimens: cranial morphology was also presumably influenced by environmental and genetic factors. The transgenic mice had larger neurocrania and an altered basicranial morphology. Although it was expected that morphological differences would be correlated with histological changes, there were few differences between wild-type and transgenic basicrania at the cellular level. An unexpected result was that increased fetal encephalization might result in a compensatory decrease in cranial ossification. The results of the human analyses showed that, contrary to expectations, a tall and rounded neurocranium was consistently correlated with a flat basicranial angle, a long and narrow foramen magnum, and a relatively small cranial base. A more narrow and elongated neuro-cranium was correlated with the opposite traits. The mouse and human specimens differed in their responses to changes in encephalization, but cranial morphology differed among small-brained and large-brained groups in both species. Because encephalization was the primary difference between transgenic and wild-type mice, traits seen in transgenic mice can be considered to be caused by the increased encephalization, either directly as a result of the larger brain size or indirectly as a result of correlated changes in other aspects of cranial morphology.

TABLE OF CONTENTS

CHAPTER 1: INTRODUCT ION

.............................................................................................. 11

A. Objectives and

Expected Significance of this Study

........................................................... 11

B. Relative Brain Size and Cranial Morphology

...................................................................... 14

Encephalization in Human and Primate Evolution .............................................................. 15

The Effects of Encephalizat ion on Interspecific Differences in Basicranial Flexion

.......... 27

Encephalization and Ontogeny

............................................................................................ 33

Craniofacial Dysmorphology

............................................................................................... 39

Previous Experimental Studies of Brain and Sk ull Interaction in Animal Models

............. 42

C. Contributions of This Study ................................................................................................. 47

Relevance of Experimental Model

...................................................................................... 47

Significant Gaps in Current Knowledge Addressed by this Study

...................................... 52

D. Comparisons and Predictions

.............................................................................................. 54

CHAPTER 2: MATERIALS

AND METHODS

...................................................................... 57

A. Specimens

............................................................................................................................ 57

Mouse Specimens

................................................................................................................ 57

Human Specimens

............................................................................................................... 59

B. Data Acquisition

.................................................................................................................. 64

Mouse Specimens

................................................................................................................ 64

Human Specimens

............................................................................................................... 77

C. Statistical Analyses

.............................................................................................................. 82

Metric Dimensions

............................................................................................................... 82

Geometric Morphometrics

................................................................................................... 83

Histology and Immunohistochemistry

................................................................................. 85

Measurement Error

.............................................................................................................. 85

D. Comparisons

........................................................................................................................ 89

CHAPTER 3: MOUSE RES ULTS

............................................................................................ 90

A. Metric Dimensions

.............................................................................................................. 90

Somatic and Postcranial Development

................................................................................ 91

Absolute Brain Size, Relative Brain Size, and Crania l Ossification

................................... 94

Linear Dimensions of the Skull

......................................................................................... 100

Angular Dimensions of the Skull

...................................................................................... 105

Correlation Analysis

.......................................................................................................... 110

7 B. Geometric Morphomet rics

................................................................................................. 115

All Landmarks

................................................................................................................... 116

Midline Landmarks

............................................................................................................ 121

Basicranial Landmarks

...................................................................................................... 125

C. Histology and Immunohistochemistry

............................................................................... 129

D. Summary of Results

.......................................................................................................... 134

Metric Dimensions

............................................................................................................. 134

Geometric Morphometrics

................................................................................................. 140

Histology and Immunohistochemistry

............................................................................... 143

CHAPTER 4:

HUMAN RESULTS

......................................................................................... 144

A. Metric Dimensions

............................................................................................................ 144

Linear Dimensions of the Skull

......................................................................................... 144

Angular Dimensions of the Skull

...................................................................................... 150

Correlation Analysis

.......................................................................................................... 152

B. Geometric Morphometrics

................................................................................................. 156

Ectocranial Landmarks

...................................................................................................... 157

Midline Landmarks

............................................................................................................ 162

Basicranial L andmarks

...................................................................................................... 166

C. Summary of Results

........................................................................................................... 170

Metric Dimensions

............................................................................................................. 170

Geometric Morphometrics

................................................................................................. 172

CHAPTER 5: DISCUSSIO N

................................................................................................... 175

A. ß - catenin Transgenic Mouse M odel

.................................................................................. 176

The Use of Mice as Model Organisms

.............................................................................. 176

Cranial Morphology in Wild- Type and Transgenic Mice

................................................. 179

Implications of These Results

............................................................................................ 194

B. Human Specimens

............................................................................................................. 199

Cranial Morphology in Normal and Pathological Humans

............................................... 199

Implications of These Results

............................................................................................ 201

C. Comparisons and Predictions

............................................................................................ 202

Comparison 1 ..................................................................................................................... 203

Comparison 2 ..................................................................................................................... 205

D. Implications for the Study of Primate Evolution

............................................................... 208

Encephalization and Cranial Morphology in Primate Evolution ....................................... 208

Why Do Primates Have Large Brains?

.............................................................................. 210

What ß - catenin Transgenic Mice Can Tell Us About Primate Evolution

......................... 213

Future Research

................................................................................................................. 215

8 E. Craniofacial Dysmorphology

............................................................................................. 216

Encephalization and Cranial Morphology in Cranial Dysmorphologies

........................... 216

How the Results of this Study Apply to the Study of Cranial Dysmorphologies

.............. 217

Future Research

................................................................................................................. 218

F. The Relationship Between Encephalization and Basicranial Flexion ................................ 220

Correlates of Basicranial Flexion

...................................................................................... 221

Basicranial Flexion i n the Human Sample

........................................................................ 229

The Relationship Between Relative Brain Size and Basicranial Flexion

.......................... 231

Future Research

................................................................................................................. 232

G. The Relationship Between Encephalization and Fa cial Morphology

............................... 233

Facial Morphology and Basicranial Flexion

...................................................................... 235

Facial Positioning and Orientation

.................................................................................... 236

Future Research

................................................................................................................. 237

H. A New “E xpensive Tissue Hypothesis”?

.......................................................................... 237

Interpretation of Ossification Results

................................................................................ 238

Ossification in Individual Litters

....................................................................................... 239

The Expensive - Tissue, Maternal Energy, and Expensive Brain Hypotheses

.................... 240

Future Research

................................................................................................................. 244

CHAPTER 6: CONCLUSIO NS

.............................................................................................. 246

A. Significance of this Research

............................................................................................ 246

B. Limitations of this Study and Future Research .................................................................. 247

C. Conclusions ........................................................................................................................ 251

REFERENCES

.......................................................................................................................... 253

9

TABLES AND FIGURES

TABLES

Table 1.1: Characteristic cranial features of anatomically modern humans

............................ 25 T able 2.1: Number of human specimens by age group and presence of pathology

................. 62 Table 2.2: Metric dimensions collected from mouse specimens .............................................. 66 Table 2.3: 3D landmarks collected from mouse specimens

..................................................... 72 Table 2.4: Histological and immunohistochemical data coll ected from mouse specimens

..... 76 Table 2.5: Metric dimensions collected from human specimens

............................................. 78 Table 2.6: 3D landmarks collected from human specimens

.................................................... 80 Table 2.7: Repeated measures in mouse specimens

................................................................. 86 Table 2.8: Repeated measures in human specimens

................................................................ 87 Tab le 3.1: Measures of overall growth and postcranial development

...................................... 92 Table 3.2: Measures of brain size and cranial ossification

....................................................... 95 Table 3.3: Linear dimensions of the skull

.............................................................................. 102 Table 3.4: Angular dimensions of the skull

........................................................................... 106 Table 3.5: Correlations between cranial dimensions and cranial base angles in mice

........... 112 Table 3.6: Correlations between cranial dimensions and cranial base angles, by genotype

.. 113 Table 3.7: Actual and predicted classification of mice using all landmarks

.......................... 118 Table 3.8: Canonical discriminant function scores for principal components 1- 6 ................. 118 Table 3.9: Actual and predicted classification of mice using midline landmarks

.................. 122 Table 3.10: Canonical discriminant function scores for principal components 1- 4 ............... 122 Table 3.11: Actual and predicted classi fication of mice using basicranial landmarks

........... 126 Table 3.12: Canonical discriminant function scores for principal components 1- 4 ............... 126 Table 3.13: Average length (mm) of basicranial components

............................................... 131 Table 3.14: Average height (mm) of basicranial components

............................................... 131 Table 3.15: Percentage of PCNA - positive cells

..................................................................... 133 Table 3.16: Percentage of ApopTag - positive cells

................................................................ 133 Table 4.1: Linear and angular dimensions of the skull

.......................................................... 145 Table 4.2: Correlations

between cranial

dimensions and cranial base angles in humans

...... 153 Table 4.3: Correlations

between cranial

dimensions and cranial base angles,

by

phenotype

. 154 Table 4.4: Actual and predicted classification of humans using ectocranial landmarks

........ 160

10 Table 4.5: Canonical discriminant function scores for principal components 1- 6 ................. 160 Table 4.6: Actual and predicted classification of humans using midline landmarks

............. 164 Table 4.7: Canonical discriminant function scores for principal components 1- 5 ................. 164 Table 4.8: Actual and predicted classification of humans using basicranial landmarks

........ 167 Table 4.9: Canonical discriminant function scores for principal components 1- 5 ................. 167 Table 5.1: Studies of the correlation between basicranial flexion and relative brain size

..... 223 FIGURES

Figure 1.1: Basicranial flexion and relative brain size

............................................................. 28 Figure 1.2: Rodent basicranial anatomy

................................................................................... 34 Figure 2.1: Angular dimensions of the mouse skull

................................................................. 68 Figure 2.2: Sample VolView window

...................................................................................... 73 Figure 3.1: Measures of overall growth and postcranial development

.................................... 93 Figure 3.2: Measures of brain size and cranial ossification ..................................................... 96 Figure 3.3: Examples of skull ossification in newborn mice

................................................... 97 Figure 3.4: Cranial ossification by litter

................................................................................... 98 Figure 3.5: Graphs of estimated marginal means

................................................................... 101 Figure 3.6: Linear dimensions of the skull

............................................................................. 103 Figure 3.7: Angular dimensions of the skull

.......................................................................... 107 Figure 3.8: Mean landmark configurations

............................................................................ 117 Figure 3.9: Principal components 1 and 2

.............................................................................. 119 Figure 3.10: Principal components 1 and 3 ............................................................................ 123 Figure 3.11: Principal components 1 and 2 ............................................................................ 127 Figure 3.12: Basicranial regions

............................................................................................. 130 Figure 3.13: Example of thicker crani al bases in transgenic mice

......................................... 132 Figure 3.14: Examples of PCNA and ApopTag stained slides

.............................................. 132 Figure 4.1: Linear dimensions of the skull

............................................................................. 148 Figure 4.2: Linear dimensions of the face

.............................................................................. 149 Figure 4.3: Angular dimensions of the skull

.......................................................................... 151 Figure 4.4: Mean landm ark configurations

............................................................................ 159 Figure 4.5: Principal components 1 and 2

.............................................................................. 161 Figure 4.6: Principal components 1 and 4

.............................................................................. 165 Figure 4.7: Principal components 1 and 2

.............................................................................. 168 Figure 5.1: Two mechanisms by which increased encephalization could affect cranial mor - phology

................................................................................................................................ 184

11

CHAPTER 1: INTRODUCT ION

A. Objectives and Expected Significance of this Study

Absolute and relative increases in brain size are often posited to influence cranial form in humans and other mammals. First, increased encephalization has been linked to t he origin of unique cranial features in a wide variety of mammalian clades. For instance, the evolution of relatively greater brain size in early Homo is thought to have left an indelible mark on the cr a- nium of subsequent hominid lineages. Second, fetal and early postnatal stages are characte r ized by remarkably high levels of encephalization as compared to adult proportions, but neither skull form nor the process of skull growth at this stage of development have been adequately studied. While brain enlar gement is a long - recognized hallmark of human modernity as well as prenatal development, explanations for correlated aspects of skull form are less clearly unde r stood. To this end, the main objective of this study is to uniquely test a hypothesis regardin g b a sicranial and neurocranial correlates of neural encephalization during prenatal growth, a period when rel a- tive brain size is predicted to have the most singular, and thus pote n tially significant, effect on skull form. The long - term goal of these analy ses is to develop a pr e natal and postnatal model of the multifactorial suite of influences on cranial ontogeny that can inform our unde r standing of the phylogenetic patterning of skull form in primates and other mammals as well as the etiology of craniofac ial pathol o gies.

12 This research employs two novel and mutually informative datasets. In order to chara c- terize prenatal patterns of human cranial development and neural encephalization, morphological data for fetal modern humans with normal and dysmorphic c onditions are analyzed. Then, these results are compared with corresponding data from a recently developed tran s genic mouse model of encephalization. These analyses integrate data on prenatal brain and skull development, a highly under - studied period whe n major structural and functional relationships are e s tablished in the skull. The transgenic mice used in this analysis (Chenn and Walsh 2002) have a constit u en t- ly a ctive β - catenin protein in their central nervous system cells, leading to an increased num ber of neural precursor cells. The β - catenin transgenic mouse model is uniquely a p propriate for the study of brain expansion in human and primate evolution because t he transgenic mice d e velop remarkably enlarged brains, particularly the surface area of the cerebral cortex, due to the i n- crease in the number of proliferating neural precursor cells. It has been posited that the dev e- l opmental expa nsion of the cortical surface of the brain in humans and other mammals is due to mutations in regulatory genes underlying increases in the number of neural progenitor cells (Fi n- lay and Darlington 1995; Rakic 1995; Buxhoeveden and Casanova 2002; Fish et al. 2008); this manner of i ncreasing brain size is similar to the process by which brain size is i n creased in the β - catenin transgenic mouse model. In this research, prenatal data for transgenic and normal mice consist of three - dimensional (3D) landmark shape data describing the cr anial vault and base obtained from ma g- netic resonance imaging (MRI) and microcomputed tomography (microCT), coupled with hi s t o- logical and immunohistochemical analyses of growing basicranial cartilage and bone. Such ev i-

13 dence addresses a significant gap in our understanding of the role of e n cephalization in the pr e- natal development and evolution of primate cranial form.

In a mature discipline like bioanthropology in which a progressively greater amount of research on morphological evolution has been performe d, significant advances, and arguably most paradigm shifts, are likely to be derived via several routes: new fossil finds which compel us to revise our notions regar ding the significance of pronounced anatomical transformations; the advent of novel techniques to address seemingly intractable problems; and the application of an a lyses which synthesize and integrate evidence concerning outstanding issues. It is these last two categories which best characterize the theoretical and methodological impact of this study on prenatal growth and encephalization in human evolution. A number of techniques, including a d- vanced imaging modalities, are used to collect data, which is then analyzed from several perspec- tives. Indeed, due to the limited nature of human specim ens, the more invasive methods to be applied to the mouse sample are intended to identify mechanisms of bone and cartilage prolifer a- tion that may similarly characterize h uman growth and development.

Following a tradition of experimental models being applie d to outstanding problems in anthropology, this study has the broader impact of incorporating data derived from highly d i- verse methods from the fields of evolutionary morphology, cell biology, and developmental b i- ology, thereby increasing our total knowledge of cranial growth, prenatal development, and brain e x pansion. Such novel evidence addresses a long- standing hypothesis regarding the mechanistic role of relative brain size in the prenatal development and the evolution of primate cranial mo r- phology.

14 T his chapter will examine the prevalence of evolutionary increases in encephalization in the taxa leading to modern humans and describe the morphological changes associated with an increased brain size. It will then discuss changes in relative brain size and the correlated an a to m- ical changes in human and primate ontogeny, human dysmorphology, and previous animal mod- els. These discussions will underscore the importance of understanding the effects of rel a tive brain size in cranial growth, evolution, and pat hology. Finally, it will discuss the relevance and expected results of this study.

Chapter 2 will discuss the two data sets used: (1) a sample of prenatal and neonatal wild- type and transgenic mice and (2) a sample of prenatal and early postnatal modern humans, some of which have pathological extremes in brain size. It will also explain the various data collection and statistical techniques that will be used. Chapters 3 and 4 will present the data collected from the mouse sample and the human sample, re spectively. Chapter 5 will discuss the r e sults of the analyses of both samples and will compare and integrate the mouse and human r e sults. Finally, Chapter 6 will offer concluding remarks and ideas for future research.

B. Relative Brain Size and Crani al Morphology

Traditionally, the skull has been divided into three main components: the basicranium (cranial base), neurocranium (cranial vault), and face. These three units have differing embr y o- nic origins, developmental processes, and functional roles (de Beer 1937; Cheverud 1982; Spe r- ber 1989; Enlow 1990; Cheverud 1996; Lieberman et al. 2000a). Although these regions are pa r tially independent of one another, they are also to some extent developmentally and function-

15 ally int e grated with one another. Th e current study explores the influence of relative brain size on the growth and morphology of the bones of the skull, focusing on the basicranium and neur o- cr a nium.

Encephalization in Human and Primate Evolution

The extremely encephalized brain is one of the most distinctive traits of modern humans. Humans have the largest relative brain size of all the extant hominoid species (Schultz 1941; Connolly 1950; Passingham 1973; Semendeferi and Damasio 2000), and modern humans are pa r ticularly notable among Homo

for their high degree of encephalization (Kappelman 1996; Ruff et al. 1997).

Encephalization refers to the amount of brain mass exceeding that expected for an an i mal of a given body size. A highly encephalized animal would have a larger than expect ed relative brain size. Encephalization is often quantified using an “encephalization quotient,” which is the ratio of the average brain size of a species to the expected average brain size of a species of the same taxon and body size (Jerison 1961, 1973) . The expected brain size is calculated by regres s- ing brain size on body size for a number of species. Factors such as the type of regression anal y- sis, the samples used, and the methods of measuring brain size and body size will influence the regression equation obtained, so calculating the “expected” brain size (and therefore the e nc e- pha lization quotient) can be problematic and different researchers will obtain different r e sults (Jerison 1961; Radinsky 1967; Wa nner 1971; Jerison 1973; Gould 1975; Bauchot 1978; Martin 1981, 1990). However, it is undisputed that humans are extremely encephalized.

16 Brain size can also be measured relative to cranial base length. This method of determi n- ing relative brain size is therefore dependent on how the cranial base is measured. Two mea s- ures of basicranial length that are often used in anthropological studies are (1) the sum of the di s- tance from basion to the pituitary point and the distance from the pituitary point to sphenoidale (Ross and Ravosa 1993; Ross and Henneberg 1995; Lieberman et al. 2000b; McCarthy 2001) and (2) the sum of the distance from basion to sella and the di s tance from sella to foramen ca e- cum (Lieberman et al. 2000b; McCarthy 2001; Jeffery and Spoor 2002; Jeffery 2003; Ross et al. 2004). In addit ion to having large brains relative to body size, humans also have large brains relative to basicranial length. Ross and Henneberg (1995) calculated the index of relative e nc e- phalization (IRE; cube root of endocranial volume divided by the basicranial len gth) for mo d ern humans and several Homo specimens. They found that modern humans had an average IRE of 1.65, larger than the A. africanus , H. erectus , or archaic H. sapiens

specimens that they mea s- ured.

Increases in both relative and absolute brain size have been documented throughout the evolution of the genus Homo (Falk 1987; Leigh 1992; Ruff et al. 1997; Rightmire 2004). Mor e- over, an increase in relative brain size has characterized the evolution of a num ber of mammalian groups: eutherians, primates, anthropoids, hominids, and Homo

all have been cha r acterized by spectacular shifts in brain expansion, and such increases have been linked to changes in the mo r- phology of the skull.

Mammals and primates:

Mammals appeared in the Late Triassic, but the fir st well - represented mammals appeared in the Early Jurassic, about 200 million years ago. Although fo s- sil finds are identified as mammals by a non - neural trait (jaw morphology; Kielan - Jaworowska et

17 al. 2004; Benton 2005), the earliest mammals had an enlarg ed relative brain size and a two - fold i ncrease in the encephalization quotient compared to their non- mammalian ancestors (Jerison 1973; Hopson 1979; Kielan- Jaworowska 1986; Kielan- Jaworowska et al. 2004). Early mamm a- l ian brains developed a new area of cor tex (the neoco r tex) above the original cortical area, which led to the great expansion in brain size (Martin 1990). Modern mammals have vastly larger brains relative to their body weight when compared with re ptiles and amphibians, and the great increase i n brain size is mainly due to their expanded cerebral hemispheres (Jerison 1973; Eise n- berg 1981; Martin 1990). Although early mammals had large brains compared to their ancestors, they had smaller brains relative to their body size when compared with modern mammals (Jerison 1961). Brain size has increased since the Tertiary period in mammals and birds, but it has not increased in re p- tiles over the same time period (Jerison 1969). There is a strong positive correlation between brain size and body size wit hin large sa m- ples of animals (Jerison 1961, 1973; Martin 1981; Harvey and Krebs 1990; Schoenemann 2004) 1

1

Brain size and body size are related exponentially, using the formula E = kP a , where E

is brain weight, P

is body weight, and k

and a

are constants ( k

is the allometric coefficient and a

is the allometric exponent; Martin

1981). This is equivalent to the fo r mula log(E) = a*log(P) + b , where b = log(k) .

. However, this relationship is not necessarily causal. In these statistical analyses, body size might be acting as a proxy for some other, unidentifi ed, variable that is causally linked with brain size (Harvey and Krebs 1990). Two possible factors are body surface area and basal met a- bolic rate. Jerison (1973, 1985) believed that body surface area was responsible for the correl a- tion between body size and brain size. His data, which included a sample of mammals, birds, fish, and reptiles (Jerison 1973), showed that brain weight scales allometrically with body weight

18 with a allometric exponent of 0.67, the same exponent that relates surface area to volu me. Ma r- tin (1981) examined birds, reptiles, and placental mammals separately and found that the all om e- tric exponents relating body size and brain size were significantly different than 0.67. The r e- gressions for birds and reptiles had exponents of 0.58 and 0.54, respe c tively, but the regression for placental mammals had an allometric exponent of 0.76, a value not significantly different than the exponent relating body size and basal metabolic rates in mammals. Martin believed that this indicated a relatio nship be tween brain size and the metabolic rate of the mother in placental mammals. Schoenemann (2004) found that there was a strong correlation between central ner v- ous system weight and fat - free weight (the weight of bones, muscles, and other components of lean body mass) in a sample of mammals. His results su pport Martin’s findings since fat - free weight is strongly correlated with metabolic rate (Halliday et al. 1979; Ravussin et al. 1982; Je n- sen et al. 1988; Owen 1988). Primates are relatively lar ge - brained mammals, although there is some overlap between primates and other placental mammals in terms of brain size relative to body size (Martin 1990; Benton 2005). Primate relative brain sizes follow a common mammalian scaling pattern; ho w- ever, prima tes tend to have a larger brain size at a given body size as compared to other ma m- mals (Ma r tin 1990).

Undisputed primates (Adapidae and Omomyidae) appear at the beginning of the Eocene and have larger, more rounded braincases compared with the plesiadapif orms (a clade widely thought of as a sister taxon to primates) that appeared in the Paleocene (Rose 1995; Fleagle 1999; Bloch and Boyer 2002). Increased relative brain size in basal primates is related to a unique combination of arboreality, precociality and small body size (Shea 1987) as well as ne u r-

19 al specializ a tions for greater visual acuity (Allman 1977, 1982; Cartmill 1992; Barton 1998). The increased brain size of primates was accompanied by other changes in cranial morphology: the early primates ha d shorter snouts, smaller infraorbital foramina, a postorbital bar, and i n- creased orbital convergence and frontality when compared to their non- primate ancestors (Car t- mill 1992; Rose 1995; Fleagle 1999; Ravosa et al. 2000; Barton 2004; Ravosa et al. 2006). Within primates, a relativ e ly larger brain appears to be associated with a more glob u lar cranial vault, a vertical forehead, a rounded occipital region, and greater basicranial flexion (Weid e- nreich 1941; Enlow 1990; Ross and Ravosa 1993). Anthropoids: A nthropoids first appear in the fossil record in the middle Eocene in Asia and Africa (Beard et al. 1994, 1996; Fleagle 1999; Simons 2004; Williams et al. 2010). Anthr o- poids differ from strepsirhines in having an expanded brain and neurocranium, increased fle x ion of the basicranium, greater frontation and convergence of the orbits, displacement of the face un- der the anterior part of the ne urocranium, and expansion of the frontal bone (Le Gros Clark 1934; Cartmill 1980; Ross 1995; Ross and Kay 2004). The increased frontation found in anthr o- poids could be the result of an anterior expansion of the neocortex (Cartmill 1970) coupled with corresponding increases in basicranial flexion (Ravosa et al. 2006). In addition to having a rel a- tively larger total brain s ize, anthropoids have a larger ne o cortex relative to total brain size than do stre psirhines (Passingham 1975, 1982).

Early anthropoids for which aspects of brain morphology are preserved, such as Aegy pt o- pithecus , had relatively larger brains compared to st repsirhines, and also had an expanded vi s ual cortex, reduced olfactory bulbs, and a well - developed central sulcus (Radinsky 1973, 1974). However, early anthropoids did not yet have a relative brain size (relative to body size) in the

20 modern a nthropoid ran ge (Radinsky 1973, 1974; Benefit and McCrossin 1997; Simons 2004). Early hominoids, like Proconsul , had relative brain sizes smaller than modern anthropoids (Fle a gle 1999), but larger com pared to other anthropoids and basal hominoids (Cameron 2004; Benton 2005). Indeed, Proconsul had a derived frontal lobe expansion leading to more anter i o r- ly positioned frontal lobes and a rounded frontal bone (Cameron 2004).

Within extant anthropoids, increases in relative brain size are correlated with several changes in cranial morphology. In haplorhines, a large brain size relative to cranial base length is assoc i ated with increased cranial base flexion and ventral deflection of the orbital axes and the upper face; however, there are no such correlations in stre p sirh ines (Ross and Ravosa 1993). A similar correlation between relative brain size and increased orbital frontation is noted during the ontogeny of extant strepsirhines and anthropoids (Ravosa et al. 2006). Increases in hominoid relative brain size are also accompanied by seemingly correlated changes in several aspects of basicranial and neurocranial shape: the inclination and position of the foramen magnum, petrous bone orientation, nuchal plane inclination, and temporonuchal crest development are all corr e- l ated with encephalization within hominoids (Strait 2001).

Full document contains 298 pages
Abstract: The lack of experimental models of brain expansion together with a dearth of information regarding fetal brain development detracts from a complete understanding of cranial integration and its relevance to the ontogenetic and interspecific patterning of the craniofacial morphology. To address this shortcoming, this study uses two datasets to examine the changes in cranial form associated with an increase in encephalization. First, mice expressing a stabilized form of β-catenin were used to isolate the effects of encephalization on the development of the basicranium and neurocranium. These transgenic mice have an increased number of neural precursors, which results in the development of an enlarged brain. Morphological differences between groups were predicted to ultimately result from variation in encephalization. Second, morphological data for fetal modern humans with normal and pathological conditions were analyzed. Like the mouse sample, the human sample was intraspecific. However, the degree of encephalization was not the only factor separating specimens: cranial morphology was also presumably influenced by environmental and genetic factors. The transgenic mice had larger neurocrania and an altered basicranial morphology. Although it was expected that morphological differences would be correlated with histological changes, there were few differences between wild-type and transgenic basicrania at the cellular level. An unexpected result was that increased fetal encephalization might result in a compensatory decrease in cranial ossification. The results of the human analyses showed that, contrary to expectations, a tall and rounded neurocranium was consistently correlated with a flat basicranial angle, a long and narrow foramen magnum, and a relatively small cranial base. A more narrow and elongated neuro-cranium was correlated with the opposite traits. The mouse and human specimens differed in their responses to changes in encephalization, but cranial morphology differed among small-brained and large-brained groups in both species. Because encephalization was the primary difference between transgenic and wild-type mice, traits seen in transgenic mice can be considered to be caused by the increased encephalization, either directly as a result of the larger brain size or indirectly as a result of correlated changes in other aspects of cranial morphology.