Biology subjects

Kanai, S. M.

Publications and source records attributed to Kanai, S. M..

2 recordsLinked to original sources

bioRxiv2024

The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development

Vertebrate jaw development is coordinated by highly conserved ligand-receptor systems such as the peptide ligand Endothelin 1 (Edn1) and Endothelin receptor type A (Ednra), which are required for patterning of lower jaw structures. The Edn1/Ednra signaling pathway establishes the identity of lower jaw progenitor cells by regulating expression of numerous patterning genes, but the intracellular signaling mechanisms linking receptor activation to gene regulation remain poorly understood. As a first step towards elucidating this mechanism, we examined the function of the Gq/11 family of G subunits in zebrafish using pharmacological inhibition and genetic ablation of Gq/11 activity and transgenic induction of a constitutively active Gq protein in edn1-/- embryos. Genetic loss of Gq/11 activity fully recapitulated the edn1-/- phenotype, with genes encoding G11 being most essential. Furthermore, inducing Gq activity in edn1-/-embryos not only restored Edn1/Ednra-dependent jaw structures and gene expression signatures but also caused homeosis of the upper jaw structure into a lower jaw-like structure. These results indicate that Gq/11 is necessary and sufficient to mediate the lower jaw patterning mechanism for Ednra in zebrafish. Summary statementGq/11 is the signaling mediator downstream of Endothelin 1 and Endothelin Receptor Type A that drives tissue patterning for all lower jaw structures in zebrafish.

developmental biology↗

bioRxiv2021

GATA3 is essential for separating patterning domains during facial morphogenesis

Neural crest cells (NCCs) within the mandibular and maxillary portions of the first pharyngeal arch are initially competent to respond to signals from either region. However, mechanisms that are only partially understood establish developmental tissue boundaries to ensure spatially correct patterning. In the Hinge and Caps model of facial development, signals from both ventral prominences, referred to as the caps, pattern the adjacent tissues while the intervening region, known as the hinge, maintains separation of the mandibular and maxillary domains. One cap signal is GATA3, a member of the GATA family of zinc-finger transcription factors with a distinct expression pattern in the ventral-most part of the mandibular and maxillary portions of the first arch. Here we show that disruption of Gata3 in mouse embryos leads to hemifacial microsomia, facial bone hypoplasia and syngnathia (bony fusion of the upper and lower jaws). These changes are preceded by gene expression changes in post-migratory NCCs around the maxillomandibular junction (the hinge). GATA3 is thus a crucial component in establishing the network of factors that functionally separate the upper and lower jaws during development. Summary StatementLoss of Gata3 leads to BMP-mediated disruption of Fgf8 expression at the maxillomandibular junction during development, resulting in later fusion of the upper and lower jaws.

developmental biology↗