Sox9b is a mediator of retinoic acid signaling restricting endocrine progenitor differentiation

作者：Huang Wei; Beer Rebecca L; Delaspre Fabien; Wang Guangliang; Edelman Hannah E; Park Hyewon; Azuma Mizuki; Parsons Michael J^*

来源：Developmental Biology, 2016, 418(1): 28-39.

DOI：10.1016/j.ydbio.2016.08.019

• Pancreas
• Progenitors
• Differentiation
• Endocrine
• Sox9

Centroacinar cells (CACs) are ductal Notch-responsive progenitors that in the larval zebrafish pancreas differentiate to form new islets and ultimately contribute to the majority of the adult endocrine mass. Uncovering the mechanisms regulating CAC differentiation will facilitate understanding how insulin producing beta cells are formed. Previously we reported retinoic acid (RA) signaling and Notch signaling both regulate larval CAC differentiation, suggesting a shared downstream intermediate. Sox9b is a transcription factor important for islet formation whose expression is upregulated by Notch signaling in larval CACs. Here we report that sox9b expression in larval CACs is also regulated by RA signaling. Therefore, we hypothesized that Sox9b is an intermediate between both RA- and Notch-signaling pathways. In order to study the role of Sox9b in larval CACs, we generated two creilox based transgenic tools, which allowed us to express full-length or truncated Sox9b in larval CACs. In this way we were able to perform spatiotemporal-controlled Sox9b gain- and loss-of-function studies and observe the subsequent effect on progenitor differentiation. Our results are consistent with Sox9b regulating CAC differentiation by being a downstream intermediate of both RA- and Notch-signaling pathways. We also demonstrate that adult zebrafish with only one functional allele of sox9b undergo accelerated beta-cell regeneration, an observation consistent with sox9b regulating CAC differentiation in adults.

• 出版日期2016-10-1