An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull

Abstract

The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure.

Why the short face? Developmental disintegration of the neurocranium drives convergent evolution in neotropical electric fishes

“…All the signaling molecules discussed above are known to perform multiple functions during development (Dworkin, Boglev, Owens, & Goldie, 2016; Harada, Sato, & Nakamura, 2016; McCarthy et al., 2016; Sudheer et al., 2016; Wada et al., 2005). It is therefore unlikely that modulation of these signaling molecules is regulated by a single gene.…”

“…Hypothesized module boundaries were defined as spatially contiguous landmark sets demarking the margins of the braincase (LM 9–17) and face, the latter of which includes the ethmoid and sphenoid regions of the neurocranium (LM 1–8) (Figure 1b). The prebraincase and braincase regions of the actinopterygian skull are defined in Patterson (1975) and Mabee and Trendler (1996) and McCarthy, Sidik, Bertrand, & Eberhart (2016). These two neurocranial regions have been shown to exhibit qualitatively distinct patterns of ontogenetic and phylogenetic shape change in some vertebrates (Emerson & Bramble, 1993), and the gymnotiform clade under investigation (Albert, 2001; Albert, Crampton, Thorsen, & Lovejoy, 2005).…”

“…Hypothesized module boundaries were defined as spatially contiguous landmark sets demarking the margins of the braincase (LM 9-17) and face, the latter of which includes the ethmoid and sphenoid regions of the neurocranium (LM 1-8) (Figure 1b). The prebraincase and braincase regions of the actinopterygian skull are defined in Patterson (1975) and Mabee and Trendler (1996) and McCarthy, Sidik, Bertrand, & Eberhart (2016).…”

“…This species was also found to be highly integrated in development despite being brachycephalic. & Goldie, 2016;Harada, Sato, & Nakamura, 2016;McCarthy et al, 2016;Sudheer et al, 2016;Wada et al, 2005). It is therefore unlikely that modulation of these signaling molecules is regulated by a single gene.…”

Gene-environment interactions characterized by single embryo transcriptomics

“…Fetal alcohol syndrome (FAS) is the most severe outcome following PAE and is characterized by midfacial hypoplasia, as well as growth and neural deficits (Jones and Smith, 1973). While PAE is required for the development of FASD, the teratogenic effects of ethanol are modulated by genetics (McCarthy et al, 2016). Genetics play a significant role as evidenced by human twin studies.…”