Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2
Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2
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DOI：
10.1242/dev.053694
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发表时间：
2011-03-01
期刊：
影响因子：
4.6
通讯作者：
Sun, Xin
中科院分区：
文献类型：
--
作者：
Domyan, Eric T.;Ferretti, Elisabetta;Sun, Xin
哺乳动物的前肠产生位于背侧的食管和胃以及位于腹侧的气管和肺。共同前肠管及其衍生器官的正确模式和形态发生对于出生时生物体的生存能力至关重要。在这里，我们表明，条件失活的BMP I型受体基因Bmpr 1a和Bmpr 1 B（Bmpr 1a;B）在腹侧内胚层导致气管发育不全和异位的初级支气管。对这些突变体的分子分析揭示了腹侧内胚层标记物NKX 2 -1的减少和背侧标记物SOX 2和P63扩展到预期的气管和初级支气管。随后的遗传实验表明，经典WNT信号的激活，以前显示诱导异位呼吸的命运，否则野生型小鼠，是不能促进呼吸的命运在Bmpr 1a; B的情况下。此外，我们发现Bmpr 1a;B突变体中Sox 2的失活不会抑制异位肺出芽，但会拯救气管形成和NKX 2 -1表达。总之，我们的数据表明，通过BMPR 1A;B的信号传导在早期呼吸发育中至少起两个作用：第一，它通过抑制Sox 2促进气管形成;第二，它限制肺芽起始的位点。
The mammalian foregut gives rise to the dorsally located esophagus and stomach and the ventrally located trachea and lung. Proper patterning and morphogenesis of the common foregut tube and its derived organs is essential for viability of the organism at birth. Here, we show that conditional inactivation of BMP type I receptor genes Bmpr1a and Bmpr1b ( Bmpr1a;b) in the ventral endoderm leads to tracheal agenesis and ectopic primary bronchi. Molecular analyses of these mutants reveal a reduction of ventral endoderm marker NKX2-1 and an expansion of dorsal markers SOX2 and P63 into the prospective trachea and primary bronchi. Subsequent genetic experiments show that activation of canonical WNT signaling, previously shown to induce ectopic respiratory fate in otherwise wild-type mice, is incapable of promoting respiratory fate in the absence of Bmpr1a; b. Furthermore, we find that inactivation of Sox2 in Bmpr1a;b mutants does not suppress ectopic lung budding but does rescue trachea formation and NKX2-1 expression. Together, our data suggest that signaling through BMPR1A;B performs at least two roles in early respiratory development: first, it promotes tracheal formation through repression of Sox2; and second, it restricts the site of lung bud initiation.