LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum
LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum
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DOI：
10.1073/pnas.0705464104
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发表时间：
2007-08-07
影响因子：
11.1
通讯作者：
Westphal, Heiner
中科院分区：
文献类型：
--
作者：
Zhao, Yangu;Kwan, Kin-Ming;Westphal, Heiner
浦肯野细胞是形成小脑神经回路的主要神经元类型之一，对运动和姿势的精细控制至关重要。在发育过程中，浦肯野细胞也参与了颗粒细胞（小脑中另一种主要的神经元类型）祖细胞增殖的调节。控制浦肯野细胞从其早期前体分化的过程尚不清楚。在这里，我们报道了两个密切相关的lim - homobox基因，Lhx1和Lhx5，在发育中的浦肯野细胞退出细胞周期并迁移出小脑室区后不久就表达出来。缺乏Lhx1和Lhx5功能的双突变小鼠浦肯野细胞数量严重减少。此外，Ldb1（编码所有lim同源结构域蛋白的辅助因子）的靶向失活导致了类似的表型。因此，我们的研究提供了证据，证明这些转录调节因子对于控制发育中的哺乳动物小脑中的浦肯野细胞分化至关重要。
Purkinje cells are one of the major types of neurons that form the neural circuitry in the cerebellum essential for fine control of movement and posture. During development, Purkinje cells also are critically involved in the regulation of proliferation of progenitors of granule cells, the other major type of neurons in the cerebellum. The process that controls differentiation of Purkinje cells from their early precursors is poorly understood. Here we report that two closely related LIM-homeobox genes, Lhx1 and Lhx5, were expressed in the developing Purkinje cells soon after they exited the cell cycle and migrated out of the cerebellar ventricular zone. Double-mutant mice lacking function of both Lhx1 and Lhx5 showed a severe reduction in the number of Purkinje cells. In addition, targeted inactivation of Ldb1, which encodes a cofactor for all LIM-homeodomain proteins, resulted in a similar phenotype. Our studies thus provide evidence that these transcription regulators are essential for controlling Purkinje cell differentiation in the developing mammalian cerebellum,