Ledonne Fanny, Orduz David, Mercier Judith, Vigier Lisa, Grove Elisabeth A, Tissir Fadel, Angulo Maria Cecilia, Pierani Alessandra, Coppola Eva
Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris Cedex 13, France.
INSERM U1128, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
Cell Rep. 2016 Dec 20;17(12):3133-3141. doi: 10.1016/j.celrep.2016.11.074.
Cajal-Retzius cells (CRs), the first-born neurons in the developing cerebral cortex, coordinate crucial steps in the construction of functional circuits. CRs are thought to be transient, as they disappear during early postnatal life in both mice and humans, where their abnormal persistence is associated with pathological conditions. Embryonic CRs comprise at least three molecularly and functionally distinct subtypes: septum, ventral pallium/pallial-subpallial boundary (PSB), and hem. However, whether subtype-specific features exist postnatally and through which mechanisms they disappear remain unknown. We report that CR subtypes display unique distributions and dynamics of death in the postnatal mouse cortex. Surprisingly, although all CR subtypes undergo cell death, septum, but not hem, CRs die in a Bax-dependent manner. Bax-inactivated rescued septum-CRs maintain immature electrophysiological properties. These results underlie the existence of an exquisitely refined control of developmental cell death and provide a model to test the effect of maintaining immature circuits in the adult neocortex.
卡哈尔-雷茨细胞（CRs）是发育中的大脑皮层中最早产生的神经元，它们协调功能回路构建中的关键步骤。CRs被认为是短暂存在的，因为它们在小鼠和人类出生后的早期生活中会消失，其异常持续存在与病理状况相关。胚胎期的CRs至少包括三种分子和功能上不同的亚型：隔区、腹侧 pallium/pallial-基底前脑边界（PSB）和脑半球。然而，出生后是否存在亚型特异性特征以及它们通过何种机制消失仍不清楚。我们报告说，CR亚型在出生后的小鼠皮层中表现出独特的分布和死亡动态。令人惊讶的是，尽管所有CR亚型都会经历细胞死亡，但隔区CRs而非脑半球CRs以Bax依赖的方式死亡。Bax失活可挽救隔区CRs，使其维持未成熟的电生理特性。这些结果揭示了对发育性细胞死亡存在精确精细控制，并提供了一个模型来测试在成年新皮层中维持未成熟回路的效果。
