Heather A. Jamniczky

Deciphering the Palimpsest: Studying the Relationship Between Morphological Integration and Phenotypic Covariation

Organisms represent a complex arrangement of anatomical structures and individuated parts that must maintain functional associations through development. This integration of variation between functionally related body parts and the modular organization of development are fundamental determinants of their evolvability. This is because integration results in the expression of coordinated variation that can create preferred directions for evolutionary change, while modularity enables variation in a group of traits or regions to accumulate without deleterious effects on other aspects of the organism. Using our own work on both model systems (e.g., lab mice, avians) and natural populations of rodents and primates, we explore in this paper the relationship between patterns of phenotypic covariation and the developmental determinants of integration that those patterns are assumed to reflect. We show that integration cannot be reliably studied through phenotypic covariance patterns alone and argue that the relationship between phenotypic covariation and integration is obscured in two ways. One is the superimposition of multiple determinants of covariance in complex systems and the other is the dependence of covariation structure on variances in covariance-generating processes. As a consequence, we argue that the direct study of the developmental determinants of integration in model systems is necessary to fully interpret patterns of covariation in natural populations, to link covariation patterns to the processes that generate them, and to understand their significance for evolutionary explanation.

Spatial packing, cranial base angulation, and craniofacial shape variation in the mammalian skull: testing a new model using mice

The hypothesis that variation in craniofacial shape within and among species is influenced by spatial packing has a long history in comparative anatomy, particularly in terms of primates. This study develops and tests three alternative models of spatial packing to address how and to what extent the cranial base angle is influenced by variation in brain and facial size. The models are tested using mouse strains with different mutations affecting craniofacial growth. Although mice have distinctive crania with small brains, long faces, and retroflexed cranial bases, the results of the study indicate that the mouse cranial base flexes to accommodate larger brain size relative to cranial base length. In addition, the mouse cranial base also extends, but to a lesser degree, to accommodate larger face size relative to cranial base length. In addition, interactions between brain size, face size, and the widths and lengths of the components of the cranial base account for a large percentage of variation in cranial base angle. The results illustrate the degree to which the cranial base is centrally embedded within the covariation structure of the craniofacial complex as a whole.

Epigenetic integration of the developing brain and face

The integration of the brain and face and to what extent this relationship constrains or enables evolutionary change in the craniofacial complex is an issue of long‐standing interest in vertebrate evolution. To investigate brain‐face integration, we studied the covariation between the forebrain and midface at gestational days 10–10.5 in four strains of laboratory mice. We found that phenotypic variation in the forebrain is highly correlated with that of the face during face formation such that variation in the size of the forebrain correlates with the degree of prognathism and orientation of the facial prominences. This suggests strongly that the integration of the brain and face is relevant to the etiology of midfacial malformations such as orofacial clefts. This axis of integration also has important implications for the evolutionary developmental biology of the mammalian craniofacial complex. Developmental Dynamics 240:2233–2244, 2011.

A COMPARISON OF COVARIANCE STRUCTURE IN WILD AND LABORATORY MUROID CRANIA

Mutations have the ability to produce dramatic changes to covariance structure by altering the variance of covariance-generating developmental processes. Several evolutionary mechanisms exist that may be acting interdependently to stabilize covariance structure, despite this developmental potential for variation within species. We explore covariance structure in the crania of laboratory mouse mutants exhibiting mild-to-significant developmental perturbations of the cranium, and contrast it with covariance structure in related wild muroid taxa. Phenotypic covariance structure is conserved among wild muroidea, but highly variable and mutation-dependent within the laboratory group. We show that covariance structures in natural populations of related species occupy a more restricted portion of covariance structure space than do the covariance structures resulting from single mutations of significant effect or the almost nonexistent genetic differences that separate inbred mouse strains. Our results suggest that developmental constraint is not the primary mechanism acting to stabilize covariance structure, and imply a more important role for other mechanisms.

Rediscovering Waddington in the post‐genomic age

Conrad Hal Waddington was a revolutionary interdisciplinary thinker well ahead of his time. Many of his ideas have been subsumed into our current understanding of developmental biology [1]. His pioneering theories, first published in the mid-20th century, continue to find validation 50 years later in the molecular era of developmental genetics [2]. Among his many contributions, Waddington [3] introduced the term epigenetics to describe the full variety of emergent developmental phenomena above the level of the genome, and elegantly expressed these ideas in the form of his widely recognised and explicitly evolutionary epigenetic landscape metaphor [3]. These emergent phenomena bridge the gap between genotype and phenotype, and comprise the epigenotype [5]. Because of this close relationship between development and evolution, it is important to grasp how such epigenetic mechanisms function. The diverse use of the term epigenetics in the subsequent literature has led to substantial disagreement about what exactly is being discussed, and at which level(s) of inquiry, despite several attempts to achieve consensus [6, 7]. In most contemporary biological contexts, epigenetics refers to chromatin modification [8]. Not only does Waddington’s more inclusive definition appear to have been largely abandoned, also the different uses of his term have coincided with the near disappearance of the original concept of epigenetics from models of evolutionary change [9]. We see this as a potentially significant problem for evolutionary biologists. In this essay our focus is on the theoretical concepts originally specified by Waddington’s epigenetics. We argue that, in this age of powerful postgenomic laboratory and bioinformatics tools, epigenetics sensu Waddington is more informative and instructive than it has been for decades. Waddington’s epigenetics has the potential to shed new light on the means by which both selectable variation and innovation, two key features of evolutionary theory, are

A NEW TURTLE FROM THE ARUNDEL CLAY FACIES (POTOMAC FORMATION, EARLY CRETACEOUS) OF MARYLAND, U.S.A.

Abstract A new paracryptodiran turtle, Arundelemys dardeni, gen. et sp. nov., is described on the basis of an isolated, nearly complete skull from the Early Cretaceous Arundel Clay facies of Maryland, USA. The basicranial region exhibits the paracryptodiran condition of a single foramen for the canalis caroticus internus located midway along the basisphenoid. As revealed by CT scans, the basicranial region of Arundelemys is unusual in that the right and left canales carotici interni merge just before reaching the sella turcica and the canalis caroticus lateralis is very small or absent. A phylogenetic analysis places Arundelemys dardeni as the basal-most member of the Paracryptodira. Within the Paracryptodira, Arundelemys dardeni is most similar to Compsemys victa in general proportions.

Signals from the brain induce variation in avian facial shape.

Background: How developmental mechanisms generate the phenotypic variation that is the raw material for evolution is largely unknown. Here, we explore whether variation in a conserved signaling axis between the brain and face contributes to differences in morphogenesis of the avian upper jaw. In amniotes, including both mice and avians, signals from the brain establish a signaling center in the ectoderm (the Frontonasal ectodermal zone or “FEZ”) that directs outgrowth of the facial primordia. Results: Here we show that the spatial organization of this signaling center differs among avians, and these correspond to Sonic hedgehog (Shh) expression in the basal forebrain and embryonic facial shape. In ducks this basal forebrain domain is present almost the entire width, while in chickens it is restricted to the midline. When the duck forebrain is unilaterally transplanted into stage matched chicken embryos the face on the treated side resembles that of the donor. Conclusions: Combined with previous findings, these results demonstrate that variation in a highly conserved developmental pathway has the potential to contribute to evolutionary differences in avian upper jaw morphology. Developmental Dynamics 244:1133–1143, 2015.

Modularity in the skull and cranial vasculature of laboratory mice: implications for the evolution of complex phenotypes.

SUMMARY The generation of coordinated morphological change over time results from the interconnectedness of evolution and development. The modular architecture of development results in varying degrees of integration and independence among parts of the phenotype, and facilitates the production of phenotypic variation in complex anatomical units composed of multiple tissue types. Here we use geometric morphometrics to investigate modularity in the arterial Circle of Willis (CW) and skull of the CD‐1 laboratory mouse. We contrast a hypothesis of tight integration between these tissues with a hypothesis of more modular organization, to determine the level at which natural selection works to generate coordinated change. We report a complex pattern of covariation that indicates that the skull and CW are highly integrated and developmentally linked. Further, we report higher levels of fluctuating asymmetry in the CW than in the skull, suggesting a greater potential for lability in this tissue. These results suggest that epigenetic interactions or genetic influences on regional development are more important determinants of covariation structure than the factors that produce covariation within individual tissues or organ systems.

Cognitive load imposed by knobology may adversely affect learners' perception of utility in using ultrasonography to learn physical examination skills, but not anatomy

Ultrasonography is increasingly used for teaching anatomy and physical examination skills but its effect on cognitive load is unknown. This study aimed to determine ultrasounds perceived utility for learning, and to investigate the effect of cognitive load on its perceived utility. Consenting first‐year medical students (n = 137) completed ultrasound training that includes a didactic component and four ultrasound‐guided anatomy and physical examination teaching sessions. Learners then completed a survey on comfort with physical examination techniques (three items; alpha = 0.77), perceived utility of ultrasound in learning (two items; alpha = 0.89), and cognitive load on ultrasound use [measured with a validated nine‐point scale (10 items; alpha = 0.88)]. Learners found ultrasound useful for learning for both anatomy and physical examination (mean 4.2 ± 0.9 and 4.4 ± 0.8, respectively; where 1 = very useless and 5 = very useful). Principal components analysis on the cognitive load survey revealed two factors, “image interpretation” and “basic knobology,” which accounted for 60.3% of total variance. Weighted factor scores were not associated with perceived utility in learning anatomy (beta = 0.01, P = 0.62 for “image interpretation” and beta = −0.04, P = 0.33 for “basic knobology”). However, factor score on “knobology” was inversely associated with perceived utility for learning physical examination (beta = −0.06; P = 0.03). While a basic introduction to ultrasound may suffice for teaching anatomy, more training may be required for teaching physical examination. Prior to teaching physical examination skills with ultrasonography, we recommend ensuring that learners have sufficient knobology skills. Anat Sci Educ 8: 197–204.

Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage

Failure of facial prominence fusion causes cleft lip and palate (CL/P), a common human birth defect. Several potential mechanisms can be envisioned that would result in CL/P, including failure of prominence growth and/or alignment as well as a failure of fusion of the juxtaposed epithelial seams. Here, using geometric morphometrics, we analyzed facial outgrowth and shape change over time in a novel mouse model exhibiting fully penetrant bilateral CL/P. This robust model is based upon mutations in Tfap2a, the gene encoding transcription factor AP-2α, which has been implicated in both syndromic and non-syndromic human CL/P. Our findings indicate that aberrant morphology and subsequent misalignment of the facial prominences underlies the inability of the mutant prominences to fuse. Exencephaly also occured in some of the Tfap2a mutants and we observed additional morphometric differences that indicate an influence of neural tube closure defects on facial shape. Molecular analysis of the CL/P model indicates that Fgf signaling is misregulated in the face, and that reducing Fgf8 gene dosage can attenuate the clefting pathology by generating compensatory changes. Furthermore, mutations in either Tfap2a or Fgf8 increase variance in facial shape, but the combination of these mutations restores variance to normal levels. The alterations in variance provide a potential mechanistic link between clefting and the evolution and diversity of facial morphology. Overall, our findings suggest that CL/P can result from small gene-expression changes that alter the shape of the facial prominences and uncouple their coordinated morphogenesis, which is necessary for normal fusion.