Unique organization of the frontonasal ectodermal zone in birds and mammals

Abstract

The faces of birds and mammals exhibit remarkable morphologic diversity, but how variation arises is not well-understood. We have previously demonstrated that a region of facial ectoderm, which we named the Frontonasal Ectodermal Zone (FEZ), regulates proximo-distal extension and dorso-ventral polarity of the upper jaw in birds. In this work, we examined the equivalent ectoderm in murine embryos and determined that the FEZ is conserved in mice. However, our results revealed that fundamental differences in the organization and constituents of the FEZ in mice and chicks may underlie the distinct growth characteristics that distinguish mammalian and avian embryos during the earliest stages of development. Finally, current models suggest that neural crest cells regulate size and shape of the upper jaw, and that signaling by Bone morphogenetic proteins (Bmps) within avian neural crest helps direct this process. Here we show that Bmp expression patterns in neural crest cells are regulated by signals from the FEZ. The results of our work reconcile how a conserved signaling center that patterns growth of developing face may generate morphologic diversity among different animals. Subtle changes in the organization of gene expression patterns in the FEZ could underlie morphologic variation observed among and within species, and at extremes, variation could produce disease phenotypes.

Embryonic bauplans and the developmental origins of facial diversity and constraint

“…Although a number of pathways, such as bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wingless (WNT) (Brugmann et al, 2007), may contribute to differential growth, SHH plays a crucial role in dorsoventral patterning, midline width variation, anterior outgrowth and palatal fusion (Marcucio et al, 2005;Hu and Marcucio, 2009;Young et al, 2010). When we compared embryonic stages corresponding to the period of maximal shape convergence, we found that Shh expression was localized to the distal tip and margins of the frontonasal, maxillary and primitive oral cavity (Fig.…”

Apaf1 apoptotic function critically limits Sonic hedgehog signaling during craniofacial development

“…The frontonasal ectodermal zone is one important signaling center that regulates the morphogenesis of the upper jaw. [25][26] This signaling center, defined by the boundary between Fgf8 and Shh expression in the FNP surface ectoderm, can induce expression of Bmp2, Bmp4 and Bmp7 in the underlying mesenchyme. Bmps are known to regulate the growth of facial primordia, 26 with Bmp2-and Bmp4-regulating speciesspecific upper jaw patterning in birds.…”

“…[25][26] This signaling center, defined by the boundary between Fgf8 and Shh expression in the FNP surface ectoderm, can induce expression of Bmp2, Bmp4 and Bmp7 in the underlying mesenchyme. Bmps are known to regulate the growth of facial primordia, 26 with Bmp2-and Bmp4-regulating speciesspecific upper jaw patterning in birds. 43 Using whole-mount in situ hybridization, we determined that the expression patterns of Fgf8, Bmp2 and Bmp4 were similar in wild-type and yautja embryos ( Figure 5B and data not shown).…”

“…Precise cellular regions of Sonic hedgehog (Shh) expression in the ventral forebrain and fibroblast growth factor 8 (Fgf8) expression in the cephalic ectoderm are termed 'signaling centers' as they convey the signal to the adjacent tissue. [25][26] Directions from these signaling centers drive bone morphogenetic protein (Bmp), retinoid and wingless (Wnt) expression in the mesenchyme and induce outgrowth of the facial prominences. [27][28][29][30][31][32] Shh is important not only for establishing craniofacial signaling centers, but also for controlling proliferation and directing cell migration, 33 which make this signaling molecule a key player in craniofacial development.…”

Maternal Diet Supplementation with Methyl Donors and Increased Parity Affect the Incidence of Craniofacial Defects in the Offspring of Twisted gastrulation Mutant Mice

“…Orofacial clefting may also arise from defective BA1 development, because clefting of both palate (24,25) and lip (26,27) can derive from deficient growth of the maxillary component of BA1. Defects of midline formation, on the other hand, arise from the failure of proper patterning or signaling from the prechordal plate and ventral forebrain (28,29) and the frontonasal ectodermal zone, which direct the formation of the midline of the face (30)(31)(32).…”