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通过Fgf/Notch信号通路对器官大小进行不依赖增殖的调控。

Proliferation-independent regulation of organ size by Fgf/Notch signaling.

作者信息

Kozlovskaja-Gumbrienė Agnė, Yi Ren, Alexander Richard, Aman Andy, Jiskra Ryan, Nagelberg Danielle, Knaut Holger, McClain Melainia, Piotrowski Tatjana

机构信息

Stowers Institute for Medical Research, Kansas City, United States.

Developmental Genetics Program and Kimmel Center for Stem Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.

出版信息

Elife. 2017 Jan 13;6:e21049. doi: 10.7554/eLife.21049.

DOI:10.7554/eLife.21049
PMID:28085667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5235355/
Abstract

Organ morphogenesis depends on the precise orchestration of cell migration, cell shape changes and cell adhesion. We demonstrate that Notch signaling is an integral part of the Wnt and Fgf signaling feedback loop coordinating cell migration and the self-organization of rosette-shaped sensory organs in the zebrafish lateral line system. We show that Notch signaling acts downstream of Fgf signaling to not only inhibit hair cell differentiation but also to induce and maintain stable epithelial rosettes. Ectopic Notch expression causes a significant increase in organ size independently of proliferation and the Hippo pathway. Transplantation and RNASeq analyses revealed that Notch signaling induces apical junctional complex genes that regulate cell adhesion and apical constriction. Our analysis also demonstrates that in the absence of patterning cues normally provided by a Wnt/Fgf signaling system, rosettes still self-organize in the presence of Notch signaling.

摘要

器官形态发生依赖于细胞迁移、细胞形状变化和细胞黏附的精确协调。我们证明，Notch信号是Wnt和Fgf信号反馈回路的一个组成部分，该回路协调斑马鱼侧线系统中的细胞迁移和玫瑰花结状感觉器官的自组织。我们表明，Notch信号在Fgf信号下游起作用，不仅抑制毛细胞分化，还诱导和维持稳定的上皮玫瑰花结。异位Notch表达导致器官大小显著增加，这与增殖和Hippo信号通路无关。移植和RNA测序分析表明，Notch信号诱导调节细胞黏附和顶端收缩的顶端连接复合体基因。我们的分析还表明，在缺乏Wnt/Fgf信号系统通常提供的模式线索的情况下，玫瑰花结在Notch信号存在时仍能自组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9efa/5235355/74580d95864d/elife-21049-fig9.jpg
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