Chang Hao, Cahill Hugh, Smallwood Philip M, Wang Yanshu, Nathans Jeremy
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS Genet. 2015 Sep 29;11(9):e1005532. doi: 10.1371/journal.pgen.1005532. eCollection 2015.
Planar cell polarity (PCP) signaling controls the global orientation of surface structures, such as hairs and bristles, in both vertebrates and invertebrates. In Frizzled6(-/-) (Fz6(-/-)) mice, hair follicle orientations on the head and back are nearly random at birth, but reorient during early postnatal development to eventually generate a nearly parallel anterior-to-posterior array. We report the identification of a naturally occurring exon 5 deletion in Astrotactin2 (Astn2) that acts as a recessive genetic modifier of the Fz6(-/-) hair patterning phenotype. A genetically engineered Astn2 exon 5 deletion recapitulates the modifier phenotype. In Fz6(-/-);Astn2(ex5del/del) mice, hair orientation on the back is subtly biased from posterior-to-anterior, leading to a 180-degree orientation reversal in mature mice. These experiments suggest that Astn2, an endosomal membrane protein, modulates PCP signaling.
平面细胞极性（PCP）信号通路控制脊椎动物和无脊椎动物体表结构（如毛发和刚毛）的整体方向。在卷曲蛋白6基因敲除（Frizzled6 -/-，Fz6 -/-）小鼠中，出生时头部和背部的毛囊方向几乎是随机的，但在出生后早期发育过程中会重新定向，最终形成几乎平行的前后排列。我们报告了在星状肌动蛋白2（Astrotactin2，Astn2）中发现的一种自然发生的外显子5缺失，它作为Fz6 -/-毛发图案化表型的隐性遗传修饰因子。基因工程改造的Astn2外显子5缺失重现了修饰因子表型。在Fz6 -/-；Astn2（ex5del/del）小鼠中，背部毛发方向从后向前略有偏向，导致成熟小鼠出现180度的方向反转。这些实验表明，作为一种内体膜蛋白的Astn2可调节PCP信号通路。
