Abstract

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.

Highlights

  • Cranial neural crest cells are a highly specialized vertebratespecific cell type which give rise to diverse structures including most of the bone and cartilage of the head, face and palate

  • Because of the restriction of satb2 in the ventral arch we focused our analyses on the Edn1, Bone morphogenic protein (Bmp) and Hh pathways

  • We show that Hh and Bmp signaling are required for satb2 expression in the developing pharyngeal arches (Fig. 7)

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Summary

Introduction

Cranial neural crest cells are a highly specialized vertebratespecific cell type which give rise to diverse structures including most of the bone and cartilage of the head, face and palate. Transplantation of smad5+/+ neural crest cells into smad5 mutants rescued the expression of satb2 in the ventral pharyngeal arch (Fig. 2 C, D; n = 7/7). Satb2 is most strongly expressed in neural crest cells in the medial region of the arch that are in close proximity to the pharyngeal endoderm, a source of both Bmp and Hh signaling [8,12,53,54].

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