Sox9b is a mediator of retinoic acid signaling restricting endocrine progenitor differentiation.
Sox9b is a mediator of retinoic acid signaling restricting endocrine progenitor differentiation.
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DOI：
10.1016/j.ydbio.2016.08.019
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发表时间：
2016-10-01
影响因子：
2.7
通讯作者：
Parsons, Michael J.
中科院分区：
文献类型：
--
作者：
Huang, Wei;Beer, Rebecca L.;Delaspre, Fabien;Wang, Guangliang;Edelman, Hannah E.;Park, Hyewon;Azuma, Mizuki;Parsons, Michael J.
中心腺泡细胞（Centroacinar cells，CACs）是一种对Notch反应敏感的导管祖细胞，在斑马鱼幼鱼胰腺中分化形成新的胰岛，并最终形成大部分成体内分泌细胞。揭示调控CAC分化的机制将有助于理解胰岛素分泌β细胞是如何形成的。以前我们报道过维甲酸（RA）信号和Notch信号都调节幼虫CAC分化，这表明一个共享的下游中间体。Sox 9 b是胰岛形成的重要转录因子，其表达在幼虫CAC中通过Notch信号上调。在这里，我们报告说，sox 9 b在幼虫CACs的表达也受到RA信号的调节。因此，我们假设Sox 9 b是RA和Notch信号通路之间的中间体。为了研究Sox 9 b在幼虫CACs中的作用，我们产生了两种基于cre/lox的转基因工具，这使得我们能够在幼虫CACs中表达全长或截短的Sox 9 b。通过这种方式，我们能够进行时空控制的Sox 9 b功能获得和丧失研究，并观察对祖细胞分化的后续影响。我们的研究结果是一致的Sox 9 b调节CAC分化的RA和Notch信号通路的下游中间体。我们还证明，成年斑马鱼只有一个功能等位基因的sox 9 b进行加速β细胞再生，观察与sox 9 b调节CAC分化的成年人一致。
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 β 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 cre/lox 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 β-cell regeneration, an observation consistent with sox9b regulating CAC differentiation in adults.
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影响因子：
3.7
作者：
Dubois CL;Shih HP;Seymour PA;Patel NA;Behrmann JM;Ngo V;Sander M
通讯作者：
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影响因子：
4.6
作者：
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通讯作者：
Leach, SD
影响因子：
64.8
作者：
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通讯作者：
Edlund, H
影响因子：
5.3
作者：
Lefebvre, V;Huang, WD;deCrombrugghe, B
通讯作者：
deCrombrugghe, B
DOI：
10.1073/pnas.0704054104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Lynn, F. C.;Smith, S. B.;German, M. S.
通讯作者：
German, M. S.