Dataset Information

Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons.

ABSTRACT: Transforming growth factor beta (TGFbeta) is a potent trophic factor for midbrain dopamine (DA) neurons, but its in vivo function and signaling mechanisms are not entirely understood. We show that the transcriptional cofactor homeodomain interacting protein kinase 2 (HIPK2) is required for the TGFbeta-mediated survival of mouse DA neurons. The targeted deletion of Hipk2 has no deleterious effect on the neurogenesis of DA neurons, but leads to a selective loss of these neurons that is due to increased apoptosis during programmed cell death. As a consequence, Hipk2(-/-) mutants show an array of psychomotor abnormalities. The function of HIPK2 depends on its interaction with receptor-regulated Smads to activate TGFbeta target genes. In support of this notion, DA neurons from Hipk2(-/-) mutants fail to survive in the presence of TGFbeta3 and Tgfbeta3(-/-) mutants show DA neuron abnormalities similar to those seen in Hipk2(-/-) mutants. These data underscore the importance of the TGFbeta-Smad-HIPK2 pathway in the survival of DA neurons and its potential as a therapeutic target for promoting DA neuron survival during neurodegeneration.

SUBMITTER: Zhang J

PROVIDER: S-EPMC3578579 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons.

Zhang Jiasheng J Pho Vanee V Bonasera Stephen J SJ Holtzman Jed J Tang Amy T AT Hellmuth Joanna J Tang Siuwah S Janak Patricia H PH Tecott Laurence H LH Huang Eric J EJ

Nature neuroscience 20061210 1

Transforming growth factor beta (TGFbeta) is a potent trophic factor for midbrain dopamine (DA) neurons, but its in vivo function and signaling mechanisms are not entirely understood. We show that the transcriptional cofactor homeodomain interacting protein kinase 2 (HIPK2) is required for the TGFbeta-mediated survival of mouse DA neurons. The targeted deletion of Hipk2 has no deleterious effect on the neurogenesis of DA neurons, but leads to a selective loss of these neurons that is due to incr ...[more]

PMID: 17159989

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Dataset Information

Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons.

Publications

Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons.

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