Devenport Danelle, Fuchs Elaine
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, New York, NY 10065, USA.
Nat Cell Biol. 2008 Nov;10(11):1257-68. doi: 10.1038/ncb1784. Epub 2008 Oct 12.
Mammalian body hairs align along the anterior-posterior (A-P) axis and offer a striking but poorly understood example of global cell polarization, a phenomenon known as planar cell polarity (PCP). We have discovered that during embryogenesis, marked changes in cell shape and cytoskeletal polarization occur as nascent hair follicles become anteriorly angled, morphologically polarized and molecularly compartmentalized along the A-P axis. Hair follicle 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 show that they have an essential role in hair follicle polarization and orientation, which develop in part through non-autonomous mechanisms. Vangl2 and Celsr1 are both required for their planar localization in vivo, and physically associate in a complex in vitro. Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact.
哺乳动物的体毛沿前后（A-P）轴排列，是整体细胞极化的一个显著但了解甚少的例子，这种现象称为平面细胞极性（PCP）。我们发现，在胚胎发育过程中，随着新生毛囊沿A-P轴向前倾斜、形态极化和分子分隔，细胞形状和细胞骨架极化会发生显著变化。毛囊起始与Vangl2、Celsr1和Fzd6在胚胎表皮基底层内的不对称重新分布同时发生。此外，Vangl2和Celsr1的功能丧失突变表明，它们在毛囊极化和定向中起重要作用，这部分是通过非自主机制发展而来的。Vangl2和Celsr1在体内的平面定位都需要它们，并且在体外以复合物形式物理结合。最后，我们提供了体外证据，证明Celsr1的同型细胞内相互作用是将Vangl2和Fzd6招募到细胞-细胞接触部位所必需的。
