Abstract

Sonic hedgehog (Shh) is involved in development of many embryonic structures. This study tries assess requirement for Shh to mediate normal branchial and aortic arch development. Shh is expressed among others in the pharyngeal endoderm from st. 17. Its expression coincides with branchial arch formation, which occurs in a temporal craniocaudal gradient starting at st. 11. In embryos treated with cyclopamine, a compound that blocks the Shh response, branchial arches were reduced in form, invaded with phagocytic cells and heads of embryos were often malformed. The aortic arches form, however, their lumen, visualized with the QH1 antibody, was misshapen and sinusoidal. Injection of 5E1 hybridoma cells, which produce an antibody that blocks Shh signaling by sequestration of the ligand, has a more profound effect on branchial arch development than cyclopamine. Capillary plexus formation was inhibited, and a higher number of QH1 positive cells in the arch mesenchyme (hemangioblasts and macrophage-like cells) were observed. Numerous apoptotic cells were found in the mesenchyme, while phagocytic cells were present in meso-, ecto- and endoderm. Our observations indicate requirement for Shh signaling for branchial morphogenesis as well as cell survival in the aortic and branchial arches. Supported by MSM 0021620806; GAUK 54/203209; 1R01HD042307(NIGMS)

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