Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles.

Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles.
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DOI:
10.1038/ncb1784
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发表时间:
2008-11
影响因子:
21.3
通讯作者:
Fuchs, Elaine
Fuchs, Elaine
中科院分区:
生物学1区
文献类型:
--
作者:
Devenport, Danelle;Fuchs, Elaine

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哺乳动物体毛沿着前后轴排列,提供了一个引人注目但鲜为人知的细胞整体极化的例子,这种现象被称为平面细胞极性(PCP)。我们发现,在胚胎发生过程中,细胞形状和细胞骨架极化发生了巨大的变化,因为新生毛囊(HFs)沿着A-P轴向前倾斜,形态极化和分子区隔。有趣的是,HF的发生与胚表皮基底层中Vangl2、Celsr1和Fzd6的不对称重新分布一致。此外,Vangl2和Celsr1功能突变的缺失揭示了它们在HF极化和定向中的重要作用,这些作用在一定程度上是通过非自主机制形成的。Vangl2和Celsr1在体内的平面定位是相互需要的,并且在体外的一个复合体中存在物理关联。最后,我们在体外提供了证据,证明Celsr1细胞间的同型相互作用需要将Vangl2和Fzd6招募到细胞-细胞接触位点。
Mammalian body hairs align along the anterior-posterior axis and offer a striking but poorly understood example of global cell polarization, a phenomenon known as planar cell polarity (PCP). We’ve discovered that during embryogenesis, dramatic changes in cell shape and cytoskeletal polarization occur as nascent hair follicles (HFs) become anteriorly angled, morphologically polarized and molecularly compartmentalized along the A–P axis. Interestingly, HF initiation coincides with asymmetric redistribution of Vangl2, Celsr1 and Fzd6 within the embryonic epidermal basal layer. Moreover, loss of function mutations in Vangl2 and Celsr1 unveil their essential role in HF polarization and orientation, which develop in part, through nonautonomous mechanisms. Vangl2 and Celsr1 are mutually required for their planar localization in vivo, and physically associate in a complex in vitro. Finally, we provide evidence in vitro that homotypic interactions of Celsr1 intercellularly are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact.
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