title: Frizzled3 is required for the development of multiple axon tracts in the mouse central nervous system.
abstract: Targeted mutation of the Frizzled3 (Fz3) gene in mice has been shown to disrupt the growth and guidance of a subset of peripheral and central axons. Here we used conditional deletion of Fz3 to explore the forebrain territories in which Fz3 action is required for the development of the anterior commissure and the corticothalamic, corticospinal, and thalamocortical tracts. Experiments with region-specific deletion of Fz3 using a variety of Cre lines show that proper routing of corticothalamic and thalamocortical axons in the internal capsule requires Fz3 expression in the ventral telencephalon. The pattern of defects among forebrain axon tracts that are induced by conditional deletion of Fz3 conforms closely to the pattern previously observed with analogous conditional deletion of Celsr3, implying a close mechanistic link between Fz3 and Celsr3 in axon guidance. We further found that several central nervous system axon tracts require Fz3 function as early as embryonic day 11.5, and that Fz3 is required for pathfinding by dopaminergic and serotonergic axons in the brain and by a subset of optic tract axons. In addition, conditional deletion of Fz3 in all tissues caudal to the neck eliminates the spinothalamic tract and the transmission of somatosensory information from the spinal cord to the brain, as determined by neuroanatomic tracing and behavioral testing.
authors.affiliation: Department of Molecular Biology and Genetics.
authors.forename: Zhong L
authors.initials: ZL
authors.lastname: Hua
authors.affiliation: Department of Biological Chemistry,Department of Neuroscience,Department of Neurosurgery,Neurosurgery Pain Research Institute.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Biological Chemistry,Department of Neuroscience,Department of Neurosurgery,Neurosurgery Pain Research Institute.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caterina
authors.affiliation: Department of Molecular Biology and Genetics,Department of Neuroscience,Department of Ophthalmology, andHoward Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 jnathans@jhmi.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D051157:Frizzled Receptors / Q000172:deficiency / Q000378:metabolism*; D020868:Gene Silencing; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D013133:Spinothalamic Tracts / Q000378:metabolism / Q000473:pathology; D013687:Telencephalon / Q000378:metabolism
chemical_list: D002395:Catecholamines; D051157:Frizzled Receptors; C486339:Fzd3 protein, mouse; D012701:Serotonin
keywords: Cre/loxP; planar cell polarity