Department of Pathology, Health Science Center, State University of New York at Stony Brook, Stony Brook, NY, USA.
Cell Death Differ. 2010 Dec;17(12):1816-29. doi: 10.1038/cdd.2010.131.
The p53 family member p73 is essential for brain development, but its precise role and scope remain unclear. Global p73 deficiency determines an overt and highly penetrant brain phenotype marked by cortical hypoplasia with ensuing hydrocephalus and hippocampal dysgenesis. The ΔNp73 isoform is known to function as a prosurvival factor of mature postmitotic neurons. In this study, we define a novel essential role of p73 in the regulation of the neural stem cell compartment. In both embryonic and adult neurogenesis, p73 has a critical role in maintaining an adequate neurogenic pool by promoting self-renewal and proliferation and inhibiting premature senescence of neural stem and early progenitor cells. Thus, products of the p73 gene locus are essential maintenance factors in the central nervous system, whose broad action stretches across the entire differentiation arch from stem cells to mature postmitotic neurons.
p53 家族成员 p73 对大脑发育至关重要，但它的确切作用和范围仍不清楚。全局 p73 缺乏决定了明显且高外显率的脑表型，其特征是皮质发育不全，随后发生脑积水和海马发育不良。已知 ΔNp73 同工型作为成熟有丝分裂后神经元的生存促进因子发挥作用。在这项研究中，我们定义了 p73 在神经干细胞区室调节中的新的必需作用。在胚胎和成年神经发生中，p73 通过促进自我更新和增殖以及抑制神经干细胞和早期祖细胞的过早衰老，在维持足够的神经发生池方面发挥关键作用。因此，p73 基因座的产物是中枢神经系统中必需的维持因子，其广泛的作用贯穿整个分化过程，从干细胞到成熟的有丝分裂后神经元。
