LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum
Autor: | Kin Ming Kwan, Heiner Westphal, Woon Kyu Lee, Richard R. Behringer, Alexander Grinberg, Christina M. Mailloux, Yangu Zhao, Wolfgang Wurst |
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Rok vydání: | 2007 |
Předmět: |
Cerebellum
Cellular differentiation LIM-Homeodomain Proteins Purkinje cell Nerve Tissue Proteins Biology DNA-binding protein Mice Purkinje Cells Pregnancy medicine Animals Progenitor cell Transcription factor Homeodomain Proteins Multidisciplinary Cell Differentiation Biological Sciences LIM Domain Proteins Cell cycle Molecular biology Cell biology DNA-Binding Proteins Mice Inbred C57BL CNS development embryo mouse transcription medicine.anatomical_structure nervous system Homeobox Female Transcription Factors |
Zdroj: | Proc. Natl. Acad. Sci. U.S.A. 104, 13182-13186 (2007) |
ISSN: | 1091-6490 0027-8424 |
DOI: | 10.1073/pnas.0705464104 |
Popis: | 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. |
Databáze: | OpenAIRE |
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