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Zhao, Y.* ; Kwan, K.M.* ; Mailloux, C.M.* ; Lee, W.K.* ; Grinberg, A.* ; Wurst, W. ; Behringer, R.R.* ; Westphal, H.*

LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum.

Proc. Natl. Acad. Sci. U.S.A. 104, 13182-13186 (2007)
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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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords CNS; development; embryo; mouse; transcription; GRANULE NEURON PRECURSORS; RECEPTOR ROR-ALPHA; HOMEOBOX GENE LIM1; SONIC HEDGEHOG; DEVELOPING BRAIN; SPINAL-CORD; IN-VIVO; EXPRESSION; MICE; PROLIFERATION
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 104, Issue: 32, Pages: 13182-13186 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)