Study of the role of the transcription factor Pax6b and different signaling pathways on pancreas differentiation in zebrafish (Danio rerio)

The developmental dynamics of the zebrafish pancreas are highly similar to mammals: the organ arises from a ventral and a dorsal bud (Field et al., 2003), and the endocrine compartment produces all different hormones: insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin (Argenton et al., 1999; Biemar et al., 2001; Tiso et al., 2009). During vertebrate evolution, the signaling pathways leading to pancreas development have shown to be highly conserved. Most of the regulatory genes characterized in humans and mouse, including the master control gene Pax6, are also involved in zebrafish pancreas development, with little or no modification in their genetic interactions. Interestingly, according to literature data, several zebrafish signaling pathway mutants exhibit a pancreatic phenotype. Therefore, the zebrafish emerges as a good model to efficiently study genetic cascades involved in pancreas development. Our study aims to dissect the specific role of the transcription factor Pax6b in relation to different signaling pathways activated in the pancreatic region of zebrafish embryos and larvae. By taking advantage of a series of pathway reporter lines, maintained or generated in our laboratory, we are systematically assessing the in vivo activation of these cascades during pancreatic development, under physiological and mutant (Pax6b-deficient) conditions. Our preliminary results suggest a role for Pax6b in endocrine cell fate decision, and show activation of Notch, Bmp and Shh signaling nearby or within the endocrine compartment. In particular, Shh-responding areas appear to correspond to specific hormone-producing cells. Implications of these results in endocrine cell type formation will be presented and discussed.