An Essential Role for Frizzled5 in Neuronal Survival in the Parafascicular Nucleus of the Thalamus

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Abstract
Frizzled5 (Fz5), a putative Wnt receptor, is expressed in the retina, hypothalamus, and the parafascicular nucleus (PFN) of the thalamus. By constructingFz5alleles in which β-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 ligandin vivo, and β-catenin, a mediator of canonical Wnt signaling, are both downregulated in theFz5−/−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.