PMID:17159989

Citation	Zhang, J, Pho, V, Bonasera, SJ, Holtzman, J, Tang, AT, Hellmuth, J, Tang, S, Janak, PH, Tecott, LH and Huang, EJ (2007) Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat. Neurosci. 10:77-86
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.
Links	PubMed Online version:10.1038/nn1816
Keywords	Amphetamine/pharmacology; Analysis of Variance; Animals; Animals, Newborn; Apoptosis/physiology; Behavior, Animal; Benzazepines/pharmacology; Calcium-Binding Protein, Vitamin D-Dependent; Calcium-Binding Proteins/metabolism; Carrier Proteins/physiology; Cell Survival/physiology; Cells, Cultured; Central Nervous System Stimulants/pharmacology; Dopamine/metabolism; Dopamine Agonists/pharmacology; Embryo, Mammalian; Gene Expression Regulation, Developmental/physiology; Homeodomain Proteins/metabolism; Immunohistochemistry; Mesencephalon/cytology; Mice; Mice, Knockout; Motor Activity/drug effects; Motor Activity/genetics; Nerve Tissue Proteins/metabolism; Neurons/physiology; Protein-Serine-Threonine Kinases/deficiency; Protein-Serine-Threonine Kinases/physiology; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/physiology; Tyrosine 3-Monooxygenase/metabolism
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.