Tbr2 expression in Cajal-Retzius cells and intermediate neuronal progenitors is required for morphogenesis of the dentate gyrus.
Tbr2 expression in Cajal-Retzius cells and intermediate neuronal progenitors is required for morphogenesis of the dentate gyrus.
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DOI：
10.1523/jneurosci.4185-12.2013
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发表时间：
2013-02-27
期刊：
影响因子：
--
通讯作者：
Hevner RF
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文献类型：
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作者：
Hodge RD;Garcia AJ 3rd;Elsen GE;Nelson BR;Mussar KE;Reiner SL;Ramirez JM;Hevner RF
齿状回（DG）是一个独特的大脑皮层区域，其发育过程跨越胚胎期和出生后早期。DG发育涉及祖细胞群体的大规模重组，最终导致颗粒下区（SGZ）神经原性生态位的建立。在发育中的DG中，T-box转录因子Tbr 2在来自皮质边缘的Cajal-Retzius细胞和中间神经元祖细胞（INPs）中表达，所述皮质边缘引导祖细胞和神经元迁移到DG，所述中间神经元祖细胞（INPs）在齿状神经上皮中产生颗粒神经元。在这里，我们表明，在小鼠Tbr 2是必要的适当迁移的Cajal-Retzius细胞DG，在没有Tbr 2的情况下，海马裂的形成是异常的，导致异常发展的transshilar放射状胶质细胞支架和受损的祖细胞和神经母细胞迁移到发展中的DG。此外，Tbr 2的丢失导致迁移细胞中Cxcr 4表达降低，导致在早期胚胎发育期间颗粒神经发生的过早爆发，伴随着突变动物中细胞死亡的增加。在Tbr 2条件性基因敲除中，暂时性软膜下神经源性区的形成是异常的，并且DG中的干细胞群体在SGZ正确建立之前被耗尽。这些研究表明，Tbr 2是明确需要的DG的形态发生，并参与了这个结构的复杂的发展过程的多个方面。
The dentate gyrus (DG) is a unique cortical region whose protracted development spans the embryonic and early postnatal periods. DG development involves large-scale reorganization of progenitor cell populations, ultimately leading to the establishment of the subgranular zone (SGZ) neurogenic niche. In the developing DG, the T-box transcription factor Tbr2 is expressed in both Cajal-Retzius cells derived from the cortical hem that guide migration of progenitors and neurons to the DG, and intermediate neuronal progenitors (INPs) born in the dentate neuroepithelium that give rise to granule neurons. Here we show that in mice Tbr2 is required for proper migration of Cajal-Retzius cells to the DG, and, in the absence of Tbr2, formation of the hippocampal fissure is abnormal, leading to aberrant development of the transhilar radial glial scaffold and impaired migration of progenitors and neuroblasts to the developing DG. Furthermore, loss of Tbr2 results in decreased expression of Cxcr4 in migrating cells, leading to a premature burst of granule neurogenesis during early embryonic development accompanied by increased cell death in mutant animals. Formation of the transient subpial neurogenic zone was abnormal in Tbr2 conditional knockouts, and the stem cell population in the DG was depleted prior to proper establishment of the SGZ. These studies indicate that Tbr2 is explicitly required for morphogenesis of the DG, and participates in multiple aspects of the intricate developmental process of this structure.