Sokpor Godwin, Brand-Saberi Beate, Nguyen Huu Phuc, Tuoc Tran
Department of Human Genetics, Ruhr University Bochum, Bochum, Germany.
Department of Anatomy and Molecular Embryology, Ruhr University Bochum, Bochum, Germany.
Front Neurosci. 2022 Feb 23;16:824802. doi: 10.3389/fnins.2022.824802. eCollection 2022.
Cortical development is dependent on key processes that can influence apical progenitor cell division and progeny. Pivotal among such critical cellular processes is the intricate mechanism of cell delamination. This indispensable cell detachment process mainly entails the loss of apical anchorage, and subsequent migration of the mitotic derivatives of the highly polarized apical cortical progenitors. Such apical progenitor derivatives are responsible for the majority of cortical neurogenesis. Many factors, including transcriptional and epigenetic/chromatin regulators, are known to tightly control cell attachment and delamination tendency in the cortical neurepithelium. Activity of these molecular regulators principally coordinate morphogenetic cues to engender remodeling or disassembly of tethering cellular components and external cell adhesion molecules leading to exit of differentiating cells in the ventricular zone. Improper cell delamination is known to frequently impair progenitor cell fate commitment and neuronal migration, which can cause aberrant cortical cell number and organization known to be detrimental to the structure and function of the cerebral cortex. Indeed, some neurodevelopmental abnormalities, including Heterotopia, Schizophrenia, Hydrocephalus, Microcephaly, and Chudley-McCullough syndrome have been associated with cell attachment dysregulation in the developing mammalian cortex. This review sheds light on the concept of cell delamination, mechanistic (transcriptional and epigenetic regulation) nuances involved, and its importance for corticogenesis. Various neurodevelopmental disorders with defective (too much or too little) cell delamination as a notable etiological underpinning are also discussed.
皮质发育依赖于能够影响顶端祖细胞分裂及其后代的关键过程。在这些关键的细胞过程中，细胞脱层的复杂机制至关重要。这种不可或缺的细胞脱离过程主要涉及顶端锚定的丧失，以及高度极化的顶端皮质祖细胞有丝分裂衍生物的后续迁移。这些顶端祖细胞衍生物负责大部分皮质神经发生。已知许多因素，包括转录和表观遗传/染色质调节因子，会严格控制皮质神经上皮中的细胞附着和脱层倾向。这些分子调节因子的活性主要协调形态发生线索，以促使束缚细胞成分和外部细胞粘附分子的重塑或解体，从而导致分化细胞从脑室区退出。众所周知，细胞脱层不当常常会损害祖细胞命运决定和神经元迁移，这可能导致皮质细胞数量和组织异常，而这对大脑皮质的结构和功能是有害的。事实上，一些神经发育异常，包括异位症、精神分裂症、脑积水、小头畸形和Chudley-McCullough综合征，都与发育中的哺乳动物皮质中的细胞附着失调有关。本综述阐述了细胞脱层的概念、所涉及的机制（转录和表观遗传调控）细微差别及其对皮质发生的重要性。还讨论了各种以细胞脱层缺陷（过多或过少）为显著病因基础的神经发育障碍。
