| 2005 |
Celsr3 (ortholog of Drosophila flamingo/starry night) is required for development of major axonal fascicles in the mammalian CNS. Mice with Celsr3 inactivation show selective, marked anomalies of several major axonal tracts (anterior commissure, internal capsule, and longitudinal brainstem/spinal cord bundles), phenocopying Fzd3 inactivation, establishing Celsr3 as a core component of a PCP-like genetic pathway controlling axonal blueprint formation. |
Constitutive gene knockout in mice; in situ hybridization for co-expression; tract tracing |
Nature neuroscience |
High |
15778712
|
| 2008 |
Conditional inactivation of Celsr3 in telencephalon, ventral forebrain, or cortex demonstrated that Celsr3 functions both cell-autonomously in neurons projecting axons and non-cell-autonomously in guidepost cells that channel growing axons through the internal capsule, establishing heterotypic axon–guidepost cell interactions as a key mechanism. |
Conditional (Cre/lox) Celsr3 knockout in specific forebrain regions; axonal tract tracing (DiI) |
Science |
High |
18487195
|
| 2009 |
Celsr3 is required for tangential and radial interneuron migration in the developing mouse forebrain. In Celsr3 knockout mice, calretinin-positive interneurons accumulate at the corticostriatal boundary and are reduced in the neocortex, while calbindin-positive cell lamination is altered; NRG1 and ErbB4 expression patterns are changed in Celsr3 mutants, implicating this pathway. |
Constitutive KO with GFP knock-in reporter; immunohistochemistry; expression analysis of NRG1/ErbB4 |
Molecular and cellular biology |
Medium |
19332558
|
| 2009 |
Celsr3 acts both in cortical projection neurons (cell-autonomous role in corticospinal axon growth) and in guidepost cells of the ventral forebrain (non-cell-autonomous role guiding axons through the internal capsule), as demonstrated by region-specific conditional inactivation. |
Conditional Celsr3 knockout (Foxg1-Cre, Emx1-Cre, Dlx-Cre); DiI tract tracing |
Cerebral cortex |
High |
19349379
|
| 2010 |
Celsr2 and Celsr3 together control ependymal ciliogenesis and planar organization of cilia. Double mutant ependyma shows markedly impaired ciliogenesis leading to lethal hydrocephalus. Celsr2 single mutants show defective planar organization of cilia and disturbed membrane distribution of Vangl2 and Fzd3; double mutants show even greater disruption of Vangl2/Fzd3 membrane asymmetry. |
Celsr2/Celsr3 single and double knockout mice; immunofluorescence for PCP proteins (Vangl2, Fzd3); cilia analysis |
Nature neuroscience |
High |
20473291
|
| 2012 |
Celsr3 is required for hippocampal connectivity and pyramidal cell maturation. Conditional inactivation in the telencephalon (Foxg1-Cre) disrupts afferent and efferent hippocampal pathways and intrinsic connections, causes atrophic CA1 dendritic trees, decreased synapse density, altered LTP, and increased symmetric vs. asymmetric synapses; interneuron migration to hippocampus is preserved. |
Conditional KO (Celsr3|Foxg1 and Celsr3|Dlx); DiI tracing; electrophysiology (LTP); synapse electron microscopy; behavioral tests |
The Journal of neuroscience |
High |
23035085
|
| 2014 |
Celsr3 in motor neurons mediates pathfinding of peroneal nerve axons in the hindlimb by enabling sensitivity to attractive EphA-ephrinA reverse signaling. Celsr3-deficient motor axons respond normally to repulsive ephrinA-EphA forward signaling and GDNF but are insensitive to attractive EphA-ephrinA reverse signaling. By co-immunoprecipitation, Celsr3 physically interacts with ephrinA2, ephrinA5, Ret, GFRα1, and Frizzled3. |
Conditional KO (motor neuron-specific); retrograde axon tracing; co-immunoprecipitation in transfected cells; epistasis with Fzd3 and Vangl2 mutants |
Nature neuroscience |
High |
25108913
|
| 2014 |
Celsr2 acts redundantly with Celsr3 in forebrain axon guidance; combined Celsr2/Celsr3 inactivation mimics Fzd3 inactivation, placing all three in the same cellular pathway. Forebrain axon wiring is normal in Vangl1/Vangl2-deficient mice, demonstrating that Celsr2/3-Fzd3-dependent axon guidance is Vangl independent—mechanistically distinct from classical epithelial PCP. |
Conditional double KO (Celsr2/Celsr3) in multiple forebrain compartments; genetic epistasis with Vangl1/2 double KO; axon tracing |
PNAS |
High |
25002511
|
| 2016 |
Celsr3 and Fzd3 in Isl1-positive pioneer neurons are required to form a scaffold of early axonal projections crossing the diencephalon-telencephalon junction (DTJ). When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, pioneer projections fail to cross the DTJ, and later-growing thalamic and cortical axons cannot traverse this junction, demonstrating that Celsr3 organizes guidepost scaffold formation for thalamocortical connectivity. |
Conditional KO in Isl1-Cre cells; axon tracing (DiI); developmental time-course analysis |
Cerebral cortex |
High |
27170656
|
| 2016 |
Celsr3 and Fzd3 in immature cortical neurons (not progenitors) are required for neurons to respond to Wnt7 and upregulate Jag1, which activates Notch signaling in neural progenitor cells, thereby providing feedback that controls the timing of progenitor fate decisions (neurogenesis-to-gliogenesis transition). |
Conditional KO of Celsr3 and Fzd3 in neurons vs. progenitors; Notch pathway readouts; Jag1 expression analysis |
Nature communications |
Medium |
26939553
|
| 2017 |
Celsr3 and Vangl2 are localized at developing glutamatergic synapses (demonstrated by synaptosome fractionation and immunostaining) and co-immunoprecipitate with key synaptic proteins. Conditional KO of Celsr3 in hippocampus postnatally causes ~50% loss of glutamatergic synapses (but not inhibitory synapses) in vivo, impairs LTP-associated spatial learning and fear conditioning. Wnt5a inhibits Celsr3-mediated glutamatergic synapse formation. Conditional KO of Vangl2 has the opposite effect (increased synapse density), establishing opposing roles for Celsr3 and Vangl2 in synaptogenesis. |
Synaptosome fractionation; immunostaining; co-immunoprecipitation; conditional KO; mEPSC recording; electron microscopy; behavioral assays |
PNAS |
High |
28057866
|
| 2017 |
Celsr3 in DRG neurons is dispensable for the initial patterning of central DRG axon projections into the spinal cord but is required for fine-mapping of sensory fiber termination: conditional inactivation (Wnt1-Cre) leads to decreased CGRP-positive fiber density in lamina I and increased Parvalbumin-positive fiber invasion of the gray matter, resulting in reduced pain sensitivity and increased mechanical sensitivity. |
Conditional KO (Wnt1-Cre); DiI tracing; immunofluorescence; behavioral pain/mechanosensory tests |
Neuroscience |
Medium |
28754314
|
| 2021 |
Celsr3 physically interacts with Kif2a (a microtubule-depolymerizing kinesin) and directs the tangential migration of neuroblasts from the SVZ to the olfactory bulb by orienting their leading process. Celsr3-deficient neuroblasts show aberrant leading process branching and decreased microtubule growth rate. Conditional inactivation of Kif2a in the forebrain recapitulates the Celsr3 KO migration phenotype, placing Celsr3 upstream of Kif2a-mediated MT dynamics. |
Conditional KO (forebrain-specific); co-immunoprecipitation (Celsr3–Kif2a interaction); live imaging of neuroblast migration; microtubule dynamics analysis; Kif2a conditional KO epistasis |
Progress in neurobiology |
High |
34582949
|
| 2021 |
Celsr3 is required for Purkinje cell maturation and postsynaptic plasticity in the cerebellum. Conditional KO in postnatal Purkinje cells causes atrophic dendrites, decreased synapse number, reduced mEPSC frequency, and defective LTP and LTD. LTP requires Wnt5a/cAMP signaling through Celsr3 and Fzd3; LTD requires mGluR1/PKCα signaling and is associated with downregulated mGluR1 expression in Celsr3 cKO. |
Conditional KO in Purkinje cells; whole-cell electrophysiology; Wnt5a perfusion; cAMP agonist/antagonist pharmacology; mGluR1 agonist application; immunofluorescence |
iScience |
Medium |
34308297
|
| 2022 |
Conditional inactivation of Celsr3 in the brainstem (En1-Cre) causes 83% reduction of rubrospinal axons and 30% decrease of corticospinal axons, increased branching of dopaminergic fibers in the ventral horn, and decreased spinal motoneurons and neuromuscular junctions, establishing a cell-non-autonomous role for Celsr3 in brainstem–spinal axon tract development. |
Conditional KO (En1-Cre); axonal tracing; transsynaptic tracing; EMG; calcium imaging; motor behavioral assays |
Molecular neurobiology |
Medium |
35678978
|
| 2024 |
In zebrafish, Celsr3 (but not Celsr2) is specifically required for axon guidance of Mauthner cells and spiral fiber neurons in the acoustic startle hindbrain circuit; Celsr3 loss disrupts Mauthner axon growth and symmetric spiral fiber innervation. Celsr3 acts via its binding partner Fzd3a. This contrasts with facial branchiomotor neuron migration which requires Celsr2 but not Celsr3, establishing distinct roles for individual PCP cadherins in different neuron populations. |
Zebrafish mutant analysis; genetic epistasis (Celsr2, Celsr3, Fzd3a loss-of-function); axon imaging; behavioral acoustic startle assays |
PLoS genetics |
Medium |
39432544
|
| 2025 |
Celsr3 deficiency in mice causes upregulation of Drd3 (dopamine D3 receptor) in striosomal D1-positive neurons with altered D3 receptor distribution (lower presynaptic, higher postsynaptic). Pharmacological activation or blockade of D3 receptors respectively amplifies or diminishes tic-like behaviors in Celsr3-deficient mice, placing D3 receptor dysregulation downstream of Celsr3 loss in a striatal circuit mediating tics. Spatial transcriptomics also reveals widespread extracellular matrix abnormalities in Celsr3 mutant striatum. |
Constitutive Celsr3 mutant mice; single-nucleus transcriptomics; spatial transcriptomics; in situ hybridization; immunofluorescence; pharmacological D3 receptor manipulation; behavioral assays |
Molecular psychiatry |
Medium |
40155412
|
| 2025 |
A human Tourette disorder-associated missense variant R774H (in the fifth cadherin repeat of CELSR3) introduced into mice causes altered cortical pyramidal neuron dendritic patterning and spine distribution, mild cholinergic interneuron hyperexcitability in the sensorimotor striatum, and sensorimotor gating deficits, without gross forebrain developmental anomalies, demonstrating that a single amino acid substitution in the cadherin domain is sufficient to perturb cortico-striatal circuit function. |
Knock-in mouse model (R774H); 3D morphometric dendritic analysis; patch-clamp electrophysiology; behavioral assays (prepulse inhibition) |
International journal of molecular sciences |
Medium |
41226347
|