Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a role in controlling early axon growth and guidance processes necessary for the formation of a subset of central and peripheral major fiber tracts. Required for the development of major fiber tracts in the central nervous system, including: the anterior commissure, the corpus callosum, the thalamocortical, corticothalamic and nigrostriatal tracts, the corticospinal tract, the fasciculus retroflexus, the mammillothalamic tract, the medial lemniscus, and ascending fiber tracts from the spinal cord to the brain. In the peripheral nervous system, controls axon growth in distinct populations of cranial and spinal motor neurons, including the facial branchimotor nerve, the hypoglossal nerve, the phrenic nerve, and motor nerves innervating dorsal limbs. Involved in the migration of cranial neural crest cells. May also be implicated in the transmission of sensory information from the trunk and limbs to the brain. Controls commissural sensory axons guidance after midline crossing along the anterior-posterior axis in the developing spinal cord in a Wnt-dependent signaling pathway. Together with FZD6, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle in a beta-catenin-dependent manner. Interacts with VANGL2. Colocalizes with FZD6 at the apical face of the cell. Expressed in the cortex, diencephalon, rostral brainstem and little or no staining is seen in the striatum or cerebellum. Expressed in both hair cells and supporting cells in the utricle, saccule, cristae and the organ of Corti in the inner ear (at protein level). Highly expressed in the CNS. In skin, it is restricted to the epidermis and to the developing hair follicle. Expressed throughout the developing central nervous system (CNS). Expressed in the cortex, diencephalon, and brainstem, with the most intense staining in the striatum and trigeminal ganglia at 18 dpc (at protein level). First detected in discrete foci in the developing epidermis of 13 days old embryos, later in the hair follicle placodes of 15 days old embryos. Expressed in the ventral and lateral margins of the spinal cord from 9.5 to 13.5 dpc, where post-crossing commissural axons project longitudinally. Expressed in superior sympathetic cervical ganglia (SCG) at 14.5 and 16.5 dpc, a stage when the SCG is comprised primarily of proliferating sympathetic neuroblasts. In 17 days embryos and 1 day old newborn, expression is limited to suprabasal keratinocytes and is not seen in pelage follicles until 3 days postpartum. In 7 days old neonatal skin, expression occurs throughout the epidermis and in the outer cell layers of hair follicles. Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway. The FZ domain is involved in binding with Wnt ligands. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. Neonate knockout mice have a curly tail, flexed lower limbs, breathe irregularly and typically die within 30 min of birth. Central nervous system (CNS) shows severe defects in the development of several major axon tracts, including: a nearly complete absence of the three early most prominent axon tracts in the brain and the ventral branch of the trigeminal nerve, absence of subcortical and striatal axons, the anterior commissure, misrouting of thalamocortical axons, a nearly complete absence of the corticospinal tract, the fasciculus retroflexus, and the mammillothalamic tract, poor fasciculation of the medial lemniscus and a disorganization of axon bundles in the reticular formation, severe defect in the asymmetric rostrocaudal orientation of dopaminergic and serotonergic axons, a large reduction or complete absence of ascending spinal axon tracts in the braistem, midbrain and thalamus, peripheral nerves defect in several motor neurons, such as in the VIIth and XIIth cranial motor nerves, the phrenic nerve, and the spinal motor nerve which failed to form connections with their respective targets and display also aberrant migration of a subpopulation of cranial neural crest cells (PubMed:12351730, PubMed:24347548, PubMed:24799694). Neonate knockout mice show fewer S-phase proliferating neuroblasts, premature cell cycle exit and enhanced apoptosis in early-stage superior cervical ganglia (SCGs), and in some cases, complete absence of sympathetic innervation of several peripheral targets (PubMed:21325504). Display also impaired rostral turning by growth cones of spinal cord commissural sensory axons (PubMed:14671310). FZD3 and FZD6 double knockout embryos have a curled tail, exhibit defects in neural tube and eyelids closure, in the orientation of hair bundles on inner-ear sensory cells and die at birth (PubMed:16495441). The following conditional knockout mice display the corresponding phenotypes: dopaminergic neuron-specific shows a defect in the orientation and growth of midbrain dopaminergic axons with an absence of striatum innervation; retinal ganglion cell (RGC)-specific displays a misrouting of a subset of optic tract axons and a lack of the medial terminal nucleus (MTN) innervation; neocortex neuron-specific displays a total absence of the posterior part of the anterior commissure and aberrant axon trajectories appearing in the external capsule; ventral telencephalon neuron-specific shows corticothalamic, thalamocortical and corticospinal tracts defect to various extent; telencephalon neuron-specific exhibits the full spectrum of axon defects seen in the classical null mutant knockout mice; cholinergic neuron-specific shows an absence of cholinergic fiber tracts passing through the striatum, a defective caudal migration of neurons of the VIIth motor nucleus and a loss of motor innervation to the face, a decrease in motor innervation of the tongue by the XIIth nerve and a complete loss of cholinergic neurons in the vomeronasal organ; oligodendrocyte neuron-specific leads to the complete spectrum of motor neuron phenotypes shown by the classical mutant knockout mice; caudal and upper thorax region-specific leads to a loss of motor innervation and an atrophy of anterior compartment muscles in the lower hindlimb by the deep peroneal nerve and a nearly absence in ascending spinal sensory axons in the brainstem, midbrain and thalamus altering the ability to transmit sensory information from the trunk and limbs to the brain in postnatal life (PubMed:24347548, PubMed:24799694). Belongs to the G-protein coupled receptor Fz/Smo family.