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J Neurosci. 2008 May 28;28(22):5641-53. doi: 10.1523/JNEUROSCI.1056-08.2008.

An essential role for Frizzled5 in neuronal survival in the parafascicular nucleus of the thalamus.

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1
Departments of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

Frizzled5 (Fz5), a putative Wnt receptor, is expressed in the retina, hypothalamus, and the parafascicular nucleus (PFN) of the thalamus. By constructing Fz5 alleles in which beta-galactosidase replaces Fz5 or in which Cre-mediated recombination replaces Fz5 with alkaline phosphatase, we observe that Fz5 is required continuously and in a cell autonomous manner for the survival of adult PFN neurons, but is not required for proliferation, migration, or axonal growth and targeting of developing PFN neurons. A motor phenotype associated with loss of Fz5 establishes a role for the PFN in sensorimotor coordination. Transcripts coding for Wnt9b, the likely Fz5 ligand in vivo, and beta-catenin, a mediator of canonical Wnt signaling, are both downregulated in the Fz5(-/-) PFN, implying a positive feedback mechanism in which Wnt signaling is required to maintain the expression of Wnt signaling components. These data suggest that defects in Wnt-Frizzled signaling could be the cause of neuronal loss in degenerative CNS diseases.

PMID:
18509025
DOI:
10.1523/JNEUROSCI.1056-08.2008
[Indexed for MEDLINE]
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