Multiple developmental mechanisms regulate species-specific jaw size

Abstract

Variation in jaw size during evolution has been crucial for the adaptive radiation of vertebrates, yet variation in jaw size during development is often associated with disease. To test the hypothesis that early developmental events regulating neural crest (NC) progenitors contribute to species-specific differences in size, we investigated mechanisms through which two avian species, duck and quail, achieve their remarkably different jaw size. At early stages, duck exhibit an anterior shift in brain regionalization yielding a shorter, broader, midbrain. We find no significant difference in the total number of pre-migratory NC; however, duck concentrate their premigratory NC in the midbrain, which contributes to an increase in size of the post-migratory NC population allocated to the mandibular arch. Subsequent differences in proliferation lead to a progressive increase in size of the duck mandibular arch relative to that of quail. To test the role of pre-migratory NC progenitor number in regulating jaw size, we reduced and augmented NC progenitors. In contrast to previous reports of regeneration by NC precursors, we find that neural fold extirpation results in a loss of NC precursors. Despite this reduction in their numbers, post-migratory NC progenitors compensate, producing a symmetric and normal-sized jaw. Our results suggest that evolutionary modification of multiple aspects of NC cell biology, including NC allocation within the jaw primordia and NC-mediated proliferation, have been important to the evolution of jaw size. Furthermore, our finding of NC post-migratory compensatory mechanisms potentially extends the developmental time frame for treatments of disease or injury associated with NC progenitor loss.

Enhancer Divergence and cis-Regulatory Evolution in the Human and Chimp Neural Crest

“…Our divergently-expressed genes are known to be involved in multiple, distinct developmental processes that cooperate to influence differential allocation of CNCCs in facial primordia and, in turn, contribute to species-specific morphology (Fish et al, 2014). These processes (and associated species-biased genes) include: (i) CNCC specification (e.g.…”

A novel ciliopathic skull defect arising from excess neural crest

“…3C) and neural specific Fgf8 expression is crucial for maintaining cranial neural crest cell numbers (Fish et al, 2014, Tabler et al, 2013, Creuzet et al, 2005). We therefore asked whether reducing Fgf8 may also rescue the defective skull morphology in Fuz mutants.…”

Cichlid fishes as a model to understand normal and clinical craniofacial variation

“…Although significant advances have been made in understanding the etiology of many Mendelian craniofacial disorders (e.g., Treacher Collins Syndrome (Kadakia, et al 2014), Apert Syndrome (Wilkie, et al 1995), and Crouzon Syndrome (Reardon, et al 1994)), much less is known about the factors that contribute to complex diseases (e.g. non-syndromic cleft lip and/or palate) and normal facial variation, which result from the cumulative effects of many alleles and their interactions with the environment (Fish, et al 2014; Glazier, et al 2002; Hallgrimsson, et al 2009; Hallgrimsson, et al 2014; Hirschhorn and Daly 2005; Hochheiser, et al 2011). Even for monogenetic diseases in which the causative genes are known we still lack a comprehensive picture of the genetic, cellular, and environmental interactions that contribute to the severity of the disease (e.g., the impact of genetic background (Dixon and Dixon 2004)).…”

“…This is perhaps unsurprising, as severe genetic lesions are likely to have more prominent phenotypic defects that are easier to identify by researchers, and speaks to the power and efficiency of forward genetic screens. However, complex traits such as normal facial variation and clinical conditions like nonsyndromic cleft lip and/or palate predominantly do not result from null alleles with large effects, but rather from a compilation of small effects from many genes that act at multiple developmental stages or confer susceptibility to environmental effects (Fish, et al 2014; Glazier, et al 2002; Hallgrimsson, et al 2009; Hallgrimsson, et al 2014; Hirschhorn and Daly 2005; Hochheiser, et al 2011). In accordance with this, the overwhelming majority (>80%) of variants implicated in complex traits and diseases by genome wide association studies (GWAS) are predicted to be in non-coding regions (Hindorff, et al 2009; Khandelwal, et al 2013; Manolio 2009).…”