骨形态发生蛋白（BMP）和Wnt通过激活Cdx-Hox信号通路来决定造血细胞命运。

BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway.

作者信息

Lengerke Claudia, Schmitt Sabine, Bowman Teresa V, Jang Il Ho, Maouche-Chretien Leila, McKinney-Freeman Shannon, Davidson Alan J, Hammerschmidt Matthias, Rentzsch Fabian, Green Jeremy B A, Zon Leonard I, Daley George Q

机构信息

Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA 02115, USA.

出版信息

Cell Stem Cell. 2008 Jan 10;2(1):72-82. doi: 10.1016/j.stem.2007.10.022.

DOI:10.1016/j.stem.2007.10.022

PMID:18371423

Abstract

The formation of blood in the embryo is dependent on bone morphogenetic protein (BMP), but how BMP signaling intersects with other regulators of hematopoietic development is unclear. Using embryonic stem (ES) cells, we show that BMP4 first induces ventral-posterior (V-P) mesoderm and subsequently directs mesodermal cells toward blood fate by activating Wnt3a and upregulating Cdx and Hox genes. When BMP signaling is blocked during this latter phase, enforced expression of either Cdx1 or Cdx4 rescues hematopoietic development, thereby placing BMP4 signaling upstream of the Cdx-Hox pathway. Wnt signaling cooperates in BMP-induced hemogenesis, and the Wnt effector LEF1 mediates BMP4 activation of Cdx genes. Our data suggest that BMP signaling plays two distinct and sequential roles during blood formation, initially as an inducer of mesoderm, and later to specify blood via activation of Wnt signaling and the Cdx-Hox pathway.

摘要

胚胎中的血液形成依赖于骨形态发生蛋白（BMP），但BMP信号传导如何与造血发育的其他调节因子相互作用尚不清楚。利用胚胎干细胞（ES细胞），我们发现BMP4首先诱导腹侧后（V-P）中胚层，随后通过激活Wnt3a并上调Cdx和Hox基因，引导中胚层细胞走向血液命运。当在后期阶段阻断BMP信号传导时，Cdx1或Cdx4的强制表达可挽救造血发育，从而将BMP4信号传导置于Cdx-Hox途径的上游。Wnt信号传导在BMP诱导的造血过程中发挥协同作用，并且Wnt效应因子LEF1介导BMP4对Cdx基因的激活。我们的数据表明，BMP信号传导在血液形成过程中发挥两个不同且连续的作用，最初作为中胚层的诱导因子，后来通过激活Wnt信号传导和Cdx-Hox途径来确定血液的形成。