Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation
Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation
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DOI：
10.1242/dev.030577
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发表时间：
2009-08-01
期刊：
影响因子：
4.6
通讯作者：
Morris, Jill A.
中科院分区：
文献类型：
--
作者：
Drerup, Catherine M.;Wiora, Heather M.;Morris, Jill A.
本研究报道了斑马鱼颅神经嵴（CNC）中精神分裂症易感基因disc1（disc1）的特征和功能分析。我们的数据表明，disc1在斑马鱼CNC细胞中表达。椎间盘1的丢失导致持续的CNC细胞内侧迁移，背侧的发展中的神经上皮细胞，并阻碍迁移远离背侧的区域的神经杆。然而，一般CNC细胞运动性不受Disc1敲低的影响，因为CNC细胞的速度与野生型对应物的速度没有区别。我们确定CNC细胞迁移离开神经杆的失败与两个转录因子foxd3和sox10的表达增强相关。这些转录因子在CNC细胞中具有许多功能，包括前体库的维持、迁移开始的时机和细胞分化的诱导。我们的工作，结合以前的研究，表明这些因素的表达的延续影响CNC细胞发育的几个方面，导致颅面软骨的损失和周围颅神经胶质细胞的扩张。基于我们的数据，我们提出了一个模型，其中Disc1功能的转录抑制foxd3和sox10，从而介导CNC细胞迁移和分化。
This work reports the characterization and functional analysis of disrupted in schizophrenia 1 (disc1), a well-documented schizophrenia-susceptibility gene, in zebrafish cranial neural crest (CNC). Our data demonstrated that disc1 was expressed in zebrafish CNC cells. Loss of Disc1 resulted in persistent CNC cell medial migration, dorsal to the developing neural epithelium, and hindered migration away from the region dorsal to the neural rod. General CNC cell motility was not affected by Disc1 knockdown, however, as the speed of CNC cells was indistinguishable from that of wild-type counterparts. We determined that the failure of CNC cells to migrate away from the neural rod correlated with the enhanced expression of two transcription factors, foxd3 and sox10. These transcription factors have many functions in CNC cells, including the maintenance of precursor pools, timing of migration onset, and the induction of cell differentiation. Our work, in conjunction with previous studies, suggests that the perpetuation of expression of these factors affects several aspects of CNC cell development, leading to a loss of craniofacial cartilage and an expansion of peripheral cranial glia. Based on our data, we propose a model in which Disc1 functions in the transcriptional repression of foxd3 and sox10, thus mediating CNC cell migration and differentiation.