Insight from Frogs: Sonic Hedgehog Gene Expression and a Re‐evaluation of the Vertebrate Odontogenic Band

Abstract

While the identification of conserved processes across multiple taxa leads to an understanding of fundamental developmental mechanisms, the ways in which different animals fail to conform to common developmental processes can elucidate how evolution modifies development to result in the vast array of morphologies seen today-the developmental mechanisms that lead to anatomical variation. Odontogenesis-how teeth are initiated and formed-is well suited to the examination of both developmental conservation and phenotypic diversity. We suggest here that the study of early tooth development, the period of odontogenic band development, reveals departures from conserved mechanisms that question the role of players in the developmental process. In the earliest stages of odontogenesis, Sonic hedgehog (Shh) gene expression is interpreted as critical evidence of tooth initiation prior to any histological indication. However, a detailed examination of studies of tooth development across a wide range of taxa reveals that several vertebrate species fail to conform to the expectations of the Shh Consensus Model, calling for a reconsideration of the assumed causality of epithelial Shh in tooth initiation. We present new Shh gene expression data for an amphibian, the frog Silurana (Xenopus) tropicalis. In these animals, craniofacial and odontogenic developmental processes are more disjunct, and thereby provide a natural test of the hypothesis that Shh is immediately required for subsequent tooth development. Our results suggest that Shh expression may actually be related to the formation of the mouth rather than a required precursor to subsequent tooth formation.

16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development inXenopus laevis

“…Recent work in cell culture suggests that MOSMO acts as a negative regulator of Sonic hedgehog signaling (Shh) by degrading the Frizzled class receptor, Smoothened (Pusapati et al, 2018), and our work is the first to elucidate the in vivo cellular function of this gene in the context of vertebrate embryonic craniofacial development. The Shh pathway is known to be critical for craniofacial morphogenesis, as upregulation or downregulation of signaling can lead to aberrant NCC patterning, development, and maintenance (Abramyan, 2019;da Costa et al, 2018;Dworkin et al, 2016;Everson et al, 2017;Grieco and Hlusko, 2016;Hammond et al, 2018;Millington et al, 2017;Okuhara et al, 2019;Wang et al, 2019). Shh signaling coordinates the downstream intracellular activity of Gli TFs, which stimulate transcription of several target genes required for NCC induction and specification (Cerrizuela et al, 2018;Millington et al, 2017;Rogers and Nie, 2018).…”

16p12.1 Deletion Orthologs are Expressed in Motile Neural Crest Cells and are Important for Regulating Craniofacial Development in Xenopus laevis

“…This has recently been confirmed in zebrafish ( Camacho-Macorra et al, 2021 ). The Shh pathway is known to be critical for craniofacial morphogenesis, as upregulation or downregulation of signaling can lead to aberrant NCC patterning, development, and maintenance ( Abramyan, 2019 ; da Costa et al, 2018 ; Dworkin et al, 2016 ; Everson et al, 2017 ; Grieco and Hlusko, 2016 ; Hammond et al, 2018 ; Millington et al, 2017 ; Okuhara et al, 2019 ; Wang et al, 2019 ). This aligns well with our results demonstrating that mosmo can directly impact NCC specification, highlighting a new cell biological role for this gene.…”

Tooth germ initiation patterns in a developing dentition: An in vivo study of Xenopus laevis tadpoles

“…With the advent of molecular studies on the developing dentition there is a growing consensus that tooth initiation arises in the jaws within a morphogenetic field (Lamoureux, ) that is termed an odontogenic band (Berkovitz & Shellis, ; Fraser et al, ; Fraser, Bloomquist, & Streelman, ; Grieco, ; Grieco & Hlusko, ; Richman & Handrigan, ; Smith, Fraser, & Mitsiadis, ). This odontogenic field appears quickly across the jaw quadrant and seems to become competent for tooth germ initiation through the combinatorial epithelial expression of pitx2 and shh .…”