Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation
Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation
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DOI：
10.1073/pnas.0609184103
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发表时间：
2006-12-19
影响因子：
11.1
通讯作者：
Hamilton, Bruce A.
中科院分区：
文献类型：
--
作者：
Alcaraz, Wendy A.;Gold, David A.;Hamilton, Bruce A.
发育中的大脑中的神经干细胞和祖细胞必须在增殖更新和分化之间做出选择。这种选择的缺陷可能导致畸形或癌症，但塑造这种选择的遗传机制尚未完全了解。我们通过定位克隆表明，30-锌指转录因子Zfp 423（OAZ）是必需的图案的神经元和神经胶质前体在发育中的大脑，特别是在中线结构的发展。Zfp 423突变导致胼胝体丢失、海马减少和小脑畸形，使人联想到人类Dandy-Walker患者。在小脑内，Zfp 423在脑室和外胚层区都有表达。Zfp 423的缺失导致外胚层中颗粒细胞前体的增殖减少，特别是中线附近，以及室带源性神经元和Bergmann胶质细胞的异常分化和迁移。
Neural stem cells and progenitors in the developing brain must choose between proliferation with renewal and differentiation. Defects in navigating this choice can result in malformations or cancers, but the genetic mechanisms that shape this choice are not fully understood. We show by positional cloning that the 30-zinc finger transcription factor Zfp423 (OAZ) is required for patterning the development of neuronal and glial precursors in the developing brain, particularly in midline structures. Mutation of Zfp423 results in loss of the corpus callosum, reduction of hippocampus, and a malformation of the cerebellum reminiscent of human Dandy-Walker patients. Within the cerebellum, Zfp423 is expressed in both ventricular and external germinal zones. Loss of Zfp423 results in diminished proliferation by granule cell precursors in the external germinal layer, especially near the midline, and abnormal differentiation and migration of ventricular zone-derived neurons and Bergmann glia.