Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation

被引：89

作者：

Chalamalasetty, Ravindra B. ^{[1
]}

Garriock, Robert J. ^{[1
]}

Dunty, William C., Jr. ^{[1
]}

Kennedy, Mark W. ^{[1
]}

Jailwala, Parthav ^{[2
]}

Si, Han ^{[2
]}

Yamaguchi, Terry P. ^{[1
]}

机构：

[1] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA

[2] FNLCR, Leidos Biomed Res, CCRIFX Bioinformat Core, Frederick, MD 21702 USA

来源：

DEVELOPMENT | 2014年 / 141卷 / 22期

基金：

美国国家卫生研究院;

关键词：

bHLH transcription factor; Paraxial mesoderm; PSM; Differentiation; EMT; Motility; Wnt; Embryonic stem cell; Somite; Mouse; EPITHELIAL-MESENCHYMAL TRANSITIONS; TRANSCRIPTION FACTOR SNAIL; BETA-CATENIN GENE; MOUSE EMBRYO; STEM-CELLS; TUMOR-CELLS; EXPRESSION; TBX6; SEGMENTATION; PROGENITORS;

D O I：

10.1242/dev.110908

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neuromesodermal (NM) stem cells generate neural and paraxial presomitic mesoderm (PSM) cells, which are the respective progenitors of the spinal cord and musculoskeleton of the trunk and tail. The Wnt-regulated basic helix-loop-helix (bHLH) transcription factor mesogenin 1 (Msgn1) has been implicated as a cooperative regulator working in concert with T-box genes to control PSM formation in zebrafish, although the mechanism is unknown. We show here that, in mice, Msgn1 alone controls PSM differentiation by directly activating the transcriptional programs that define PSM identity, epithelial-mesenchymal transition, motility and segmentation. Forced expression of Msgn1 in NM stem cells in vivo reduced the contribution of their progeny to the neural tube, and dramatically expanded the unsegmented mesenchymal PSM while blocking somitogenesis and notochord differentiation. Expression of Msgn1 was sufficient to partially rescue PSM differentiation in Wnt3a(-/-) embryos, demonstrating that Msgn1 functions downstream of Wnt3a as the master regulator of PSM differentiation. Our data provide new insights into how cell fate decisions are imposed by the expression of a single transcriptional regulator.

引用

页码：4285 / 4297

页数：13

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