Embryonic origin and compartmental organization of the external genitalia.
Embryonic origin and compartmental organization of the external genitalia.
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DOI：
10.1038/srep06896
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发表时间：
2014-11-05
影响因子：
4.6
通讯作者：
Cohn MJ
中科院分区：
文献类型：
--
作者：
Herrera AM;Cohn MJ
生殖器畸形在人类中发生的频率很高，影响约1：250的活产。外生殖器发育的分子机制开始被确定;然而，产生外生殖器的细胞的起源是未知的。在这里，我们使用细胞谱系分析表明，生殖结节，阴茎和阴蒂的前体，来自两个群体的祖细胞，起源于胚胎的侧边缘，在后后肢芽和前尾的水平。在体壁闭合期间，左右外生殖器祖细胞池在腹侧中线处聚集在一起，在那里它们形成成对的生殖器鞘，从而产生生殖器结节。出乎意料的是，左外生殖器和右外生殖器祖细胞池在阴茎中形成了两个谱系限制的隔间。与以前的谱系研究肢芽，我们的研究结果表明，在骨盆水平，早期外侧中胚层区域化从内侧到外侧到背侧肢体，腹侧肢体，和外部生殖祖领域。这些发现对外生殖器的进化多样化以及外生殖器缺陷与体壁闭合中断之间的关联具有影响，如在epispadias-extrophy复合体中所见。
Genital malformations occur at a high frequency in humans, affecting ~1:250 live births. The molecular mechanisms of external genital development are beginning to be identified; however, the origin of cells that give rise to external genitalia is unknown. Here we use cell lineage analysis to show that the genital tubercle, the precursor of the penis and clitoris, arises from two populations of progenitor cells that originate at the lateral edges of the embryo, at the level of the posterior hindlimb buds and anterior tail. During body wall closure, the left and right external genital progenitor pools are brought together at the ventral midline, where they form the paired genital swellings that give rise to the genital tubercle. Unexpectedly, the left and right external genital progenitor pools form two lineage-restricted compartments in the phallus. Together with previous lineage studies of limb buds, our results indicate that, at the pelvic level, the early lateral mesoderm is regionalized from medial to lateral into dorsal limb, ventral limb, and external genital progenitor fields. These findings have implications for the evolutionary diversification of external genitalia and for the association between external genital defects and disruption of body wall closure, as seen in the epispadias-extrophy complex.