Bmp and Shh Signaling Mediate the Expression of satb2 in the Pharyngeal Arches

Kelly Sheehan-Rooney is with UT Austin, Mary E. Swartz is with UT Austin, C. Ben Lovely is with UT Austin, Michael J. Dixon is with University of Manchester, Johann K. Eberhart is with UT Austin.In human, mutation of the transcription factor SATB2 causes severe defects to the palate and jaw. The expression and sequence of SATB2 is highly conserved across vertebrate species, including zebrafish. We sought to understand the regulation of satb2 using the zebrafish model system. Due to the normal expression domains of satb2, we analyzed satb2 expression in mutants with disrupted Hh signaling or defective ventral patterning. While satb2 expression appears independent of Edn1 signaling, appropriate expression requires Shha, Smo, Smad5 and Hand2 function. Transplantation experiments show that neural crest cells receive both Bmp and Hh signaling to induce satb2 expression. Dorsomorphin- and cyclopamine-mediated inhibition of Bmp and Hh signaling, respectively, suggests that proper satb2 expression requires a relatively earlier Bmp signal and a later Hh signal. We propose that Bmp signaling establishes competence for the neural crest to respond to Hh signaling, thus inducing satb2 expression.This work was supported by United States National Institutes of Health grants DE018088 and DE020884 to J.K.E. and MRC grant (G1001601) and support from the Healing Foundation to M.J.D. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Cellular and Molecular Biolog