Gupta Sunny, Zhu Hao, Zon Leonard I, Evans Todd
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Development. 2006 Jun;133(11):2177-87. doi: 10.1242/dev.02386. Epub 2006 May 3.
The bone morphogenetic protein (BMP) signaling pathway is essential during gastrulation for the generation of ventral mesoderm, which makes it a challenge to define functions for this pathway at later stages of development. We have established an approach to disrupt BMP signaling specifically in lateral mesoderm during somitogenesis, by targeting a dominant-negative BMP receptor to Lmo2+ cells in developing zebrafish embryos. This results in expansion of hematopoietic and endothelial cells, while restricting the expression domain of the pronephric marker pax2.1. Expression of a constitutively active receptor and transplantation experiments were used to confirm that BMP signaling in lateral mesoderm restricts subsequent hemato-vascular development. The results show that the BMP signaling pathway continues to function after cells are committed to a lateral mesoderm fate, and influences subsequent lineage decisions by restricting hemato-vascular fate in favor of pronephric development.
骨形态发生蛋白(BMP)信号通路在原肠胚形成过程中对于腹侧中胚层的产生至关重要,这使得在发育后期确定该信号通路的功能成为一项挑战。我们建立了一种方法,通过在发育中的斑马鱼胚胎中将显性负性BMP受体靶向到Lmo2+细胞,在体节形成过程中特异性地破坏侧中胚层中的BMP信号。这导致造血细胞和内皮细胞的扩增,同时限制了前肾标志物pax2.1的表达域。使用组成型活性受体的表达和移植实验来证实侧中胚层中的BMP信号限制了随后的血管生成。结果表明,BMP信号通路在细胞确定为侧中胚层命运后仍继续发挥作用,并通过限制血管命运以利于前肾发育来影响随后的谱系决定。