LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum
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 majo...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 32; pp. 13182 - 13186 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
07.08.2007
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Communicated by Igor B. Dawid, National Institutes of Health, Bethesda, MD, June 11, 2007 Present address: Department of Biology, Chinese University of Hong Kong, Hong Kong, China. Author contributions: Y.Z. and K.-M.K. contribruted equally to this work; Y.Z., K.-M.K., R.R.B., and H.W. designed research; Y.Z., K.-M.K., C.M.M., W.-K.L., and A.G. performed research; W.W. contributed new reagents/analytic tools; Y.Z., K.-M.K., R.R.B., and H.W. analyzed data; and Y.Z., K.-M.K., R.R.B., and H.W. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0705464104 |