Frizzled-3 is required for the development of major fiber tracts in the rostral CNS.
Many ligand/receptor families are known to contribute to axonal growth and targeting. Thus far, there have been no reports implicating Wnts and Frizzleds in this process, despite their large numbers and widespread expression within the CNS. In this study, we show that targeted deletion of the mouse fz3 gene leads to severe defects in several major axon tracts within the forebrain. In particular, fz3(-/-) mice show a complete loss of the thalamocortical, corticothalamic, and nigrostriatal tracts and of the anterior commissure, and they show a variable loss of the corpus callosum. Peripheral nerve fibers and major axon tracts in the more caudal regions of the CNS are mostly or completely unaffected. Cell proliferation in the ventricular zone and cell migration to the developing cortex proceed normally until at least embryonic day 14. Extensive cell death in the fz3(-/-) striatum occurs late in gestation, perhaps secondary to the nearly complete absence of long-range connections. In contrast, there is little cell death, as assayed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, in the cortex. These data provide the first link between Frizzled signaling and axonal development.
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002490:Central Nervous System / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology; D051157:Frizzled Receptors; D018390:Gene Targeting; D017930:Genes, Reporter; D020287:In Situ Nick-End Labeling; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology*; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology; D009434:Neural Pathways / Q000002:abnormalities* / Q000473:pathology; D010641:Phenotype; D016548:Prosencephalon / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D012131:Respiratory Insufficiency / Q000235:genetics / Q000473:pathology
D051157:Frizzled Receptors; C486339:Fzd3 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled