Lake Blue B, Sokol Sergei Y
Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Cell Biol. 2009 Apr 6;185(1):59-66. doi: 10.1083/jcb.200807073. Epub 2009 Mar 30.
The planar cell polarity (PCP) pathway organizes the cytoskeleton and polarizes cells within embryonic tissue. We investigate the relationship between PCP signaling and cell fate determination during asymmetric division of neural progenitors (NPs) in mouse embryos. The cortex of Lp/Lp (Loop-tail) mice deficient in the essential PCP mediator Vangl2, homologue of Drosophila melanogaster Strabismus (Stbm), revealed precocious differentiation of neural progenitors into early-born neurons at the expense of late-born neurons and glia. Although Lp/Lp NPs were easily maintained in vitro, they showed premature differentiation and loss of asymmetric distribution of Leu-Gly-Asn-enriched protein (LGN)/partner of inscuteable (Pins), a regulator of mitotic spindle orientation. Furthermore, we observed a decreased frequency in asymmetric distribution of the LGN target nuclear mitotic apparatus protein (NuMa) in Lp/Lp cortical progenitors in vivo. This was accompanied by an increase in the number of vertical cleavage planes typically associated with equal daughter cell identities. These findings suggest that Stbm/Vangl2 functions to maintain cortical progenitors and regulates mitotic spindle orientation during asymmetric divisions in the vertebrate brain.
平面细胞极性（PCP）信号通路可组织细胞骨架并使胚胎组织内的细胞极化。我们研究了小鼠胚胎中神经祖细胞（NP）不对称分裂过程中PCP信号与细胞命运决定之间的关系。缺乏关键PCP介质Vangl2（果蝇斜视（Stbm）的同源物）的Lp/Lp（卷尾）小鼠的皮层显示，神经祖细胞过早分化为早出生的神经元，代价是晚出生的神经元和神经胶质细胞。尽管Lp/Lp神经祖细胞在体外易于维持，但它们显示出过早分化以及富含亮氨酸-甘氨酸-天冬酰胺的蛋白（LGN）/无柄蛋白（Pins）（一种有丝分裂纺锤体方向调节因子）不对称分布的丧失。此外，我们在体内观察到Lp/Lp皮层祖细胞中LGN靶标核有丝分裂器蛋白（NuMa）的不对称分布频率降低。这伴随着通常与相等子细胞身份相关的垂直分裂平面数量的增加。这些发现表明，Stbm/Vangl2在脊椎动物大脑的不对称分裂过程中起到维持皮层祖细胞并调节有丝分裂纺锤体方向的作用。
