Midline-derived Shh regulates mesonephric tubule formation through the paraxial mesoderm.

Midline-derived Shh regulates mesonephric tubule formation through the paraxial mesoderm.
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DOI:
10.1016/j.ydbio.2013.12.026
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发表时间:
2014-02-01
影响因子:
2.7
通讯作者:
Yamada, Gen
Yamada, Gen
中科院分区:
生物学3区
文献类型:
--
作者:
Murashima, Aki;Akita, Hiroki;Okazawa, Mika;Kishigami, Satoshi;Nakagata, Naomi;Nishinakamura, Ryuichi;Yamada, Gen

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在器官发生过程中,Sonic hedgehog(Shh)具有双重功能:Shh从中线结构发出,在早期阶段调节双侧结构的定位,而器官特异性Shh在后期阶段局部调节器官形态发生。中肾是一个短暂的胚胎肾在蝾螈,而它成为确定的成年肾脏在某些蝾螈。因此,阐明中肾形成的调控对我们理解肾脏的发育和进化具有重要意义。在Shh基因敲除(KO)突变小鼠中,中肾向中线移位,异位中肾小管(MT)存在于尾侧中肾。Hoxb 7-Cre;Shhflox/−和Sall 1CreERT 2/+;Shhflox/−小鼠胚胎中Shh的中肾特异性消融表明,中肾中表达的Shh对于中肾的发育或雄性生殖道的分化都不是必需的。此外,ShhCreERT 2/flox小鼠中Shh的阶段特异性消融表明,脊索和/或底板衍生的Shh对于调节MT的数量和位置至关重要。刺猬(Hh)响应细胞的谱系分析,并在Shh KO胚胎的基因表达分析表明,Shh调节肾基因的表达间接,可能是通过对近轴中胚层的影响。这些数据证明了中线衍生的Shh在局部组织形态发生和分化中的重要作用。
During organogenesis, Sonic hedgehog (Shh) possesses dual functions: Shh emanating from midline structures regulates the positioning of bilateral structures at early stages, whereas organ-specific Shh locally regulates organ morphogenesis at later stages. The mesonephros is a transient embryonic kidney in amniote, whereas it becomes definitive adult kidney in some anamniotes. Thus, elucidating the regulation of mesonephros formation has important implications for our understanding of kidney development and evolution. In Shh knockout (KO) mutant mice, the mesonephros was displaced towards the midline and ectopic mesonephric tubules (MTs) were present in the caudal mesonephros. Mesonephros-specific ablation of Shh in Hoxb7-Cre;Shhflox/− and Sall1CreERT2/+;Shhflox/− mice embryos indicated that Shh expressed in the mesonephros was not required for either the development of the mesonephros or the differentiation of the male reproductive tract. Moreover, stage-specific ablation of Shh in ShhCreERT2/flox mice showed that notochord- and/or floor plate-derived Shh were essential for the regulation of the number and position of MTs. Lineage analysis of hedgehog (Hh)-responsive cells, and analysis of gene expression in Shh KO embryos suggested that Shh regulated nephrogenic gene expression indirectly, possibly through effects on the paraxial mesoderm. These data demonstrate the essential role of midline-derived Shh in local tissue morphogenesis and differentiation.
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