Understanding endothelin-1 function during craniofacial development in the mouse and zebrafish

Abstract

Morphogenesis of the face and neck is driven by an intricate relay of signaling molecules and transcription factors organized into hierarchical pathways. The coordinated action of these pathways regulates the development of neural crest cells within the pharyngeal arches, resulting in proper spatiotemporal formation of bone, cartilage, and connective tissue. While the functions of many genes involved in these processes were initially elucidated through the use of knockout technology in the mouse, increasing numbers of zebrafish craniofacial mutants have led to a rapid expansion in the identification of genes involved in craniofacial development. A comparative analysis of signaling pathways involved in these processes between mouse and zebrafish holds the potential not only to pinpoint conserved and therefore crucial gene functions in craniofacial development, but also to rapidly identify and study downstream effectors. These complementary approaches will also allow rapid identification of candidate genes and gene functions disrupted in human craniofacial dysmorphologies. In this brief review, we present a comparative analysis of one molecule involved in craniofacial development, endothelin-1, a small, secreted protein that is crucial for patterning the neural crest cells that give rise to lower jaw and throat structures.