| 2011 |
TCTN2 forms a protein complex with multiple ciliopathy proteins (MKS1, TMEM216, TMEM67, CEP290, B9D1, TCTN1, CC2D2A) that co-localizes at the transition zone of primary cilia. Loss of TCTN2 causes tissue-specific defects in ciliogenesis and in the localization of select membrane-associated proteins to the cilium (including ARL13B, AC3, Smoothened, PKD2). |
Co-immunoprecipitation, co-localization at transition zone, loss-of-function mouse models with ciliary membrane composition analysis |
Nature genetics |
High |
21725307
|
| 2015 |
Super-resolution STED microscopy established that TCTN2, as a transmembrane protein, localizes at a specific axial level of the transition zone coinciding with MKS1 and RPGRIP1L, distinct from the axial position of CEP290. |
Stimulated emission depletion (STED) super-resolution microscopy with positional averaging |
Scientific reports |
Medium |
26365165
|
| 2017 |
JBTS-associated mutations in TCTN2 displace certain transition-zone proteins from their normal positions within the transition zone, as defined by two-color STORM super-resolution microscopy. TCTN2 mutant cells show disrupted transition-zone architecture with NPHP and MKS complex components forming nested nine-fold doublet rings. |
Two-colour stochastic optical reconstruction microscopy (STORM) in patient-derived or mutant cells |
Nature cell biology |
High |
28846093
|
| 2017 |
Tctn2 mutant mice exhibit holoprosencephaly, randomized heart looping, and lack of the floor plate in the neural tube, phenotypes associated with severely reduced Hedgehog (Hh) signaling and ciliogenesis. Overexpression of Tctn1 or Tctn3 in the Tctn2 gene locus cannot rescue ciliogenesis and Hh signaling defects but can rescue neural tube patterning and Gli3 processing, indicating TCTN2 has a unique and non-redundant role in ciliogenesis and Hh signaling. |
Mouse knockout models, gene replacement at endogenous locus, Gli3 processing assays, neural tube patterning markers |
Developmental biology |
High |
28800946
|
| 2018 |
CRISPR/Cas9 knockout of TCTN2 in human RPE cells causes partial transition zone damage, loss of ciliary membrane proteins, leakage of intraflagellar transport protein IFT88 from the ciliary lumen toward the basal body lumen, and cilium shortening and curving, demonstrating that TCTN2 is required for structural integrity of the transition zone gate. |
CRISPR/Cas9 knockout cell line, super-resolution and wide-field microscopy, quantitative geometric localization analysis |
Biophysical journal |
High |
29866362
|
| 2021 |
Tctn2 mutant mice display hypotelorism due to reduced Hedgehog (HH) pathway activation in the prechordal plate as early as the end of gastrulation, which precedes reduced Shh expression in the adjacent neurectoderm and increased cell death. Reducing gene dosage of the HH pathway negative regulator Ptch1 rescues midface defects in Tctn2 mutants, placing TCTN2 upstream of HH-mediated cell survival in facial midline development. |
Mouse knockout models, genetic epistasis (Tctn2 mutant × Ptch1 heterozygous), HH pathway reporters, cell death assays |
eLife |
High |
34672258
|
| 2012 |
TCTN3, a paralog of TCTN2, forms a complex at the ciliary transition zone with TCTN1 and TCTN2, and TCTN3 loss results in abnormal GLI3 processing in patient cells, consistent with roles for the entire Tectonic complex in SHH signaling transduction. |
Patient cell GLI3 processing assay, complex co-localization studies |
American journal of human genetics |
Medium |
22883145
|
| 2018 |
Knockdown of tctn2 in zebrafish disrupts cardiac looping and causes abnormal expression of left-right patterning markers lefty2 and pitx2, demonstrating a role for TCTN2 in left-right axis specification. |
Morpholino knockdown in zebrafish, cardiac looping assay, in situ hybridization for lefty2/pitx2 |
Genome medicine |
Medium |
29843777
|
| 2022 |
MXI1 (Max interacting protein 1) binds to the TCTN2 promoter to promote its transcription, and upregulated TCTN2 mediates MXI1-driven Th17/Treg imbalance in osteoarthritis; silencing TCTN2 negates the effects of MXI1 overexpression on T cell differentiation. |
Chromatin binding assay (MXI1 binding to TCTN2 promoter), loss- and gain-of-function experiments in CD4+ T cells and OA mouse model, flow cytometry for Th17/Treg proportions |
Tissue & cell |
Low |
36049372
|
| 2025 |
In human neural tube organoids, TCTN2 deficiency causes dorsal-ventral patterning defects, and this phenotype could be modeled and rescued, demonstrating a role for TCTN2 in SHH-dependent D-V neural tube patterning in a human cellular context. |
hPSC-derived neural tube organoids with TCTN2 mutation, single-cell transcriptomics, rescue assays |
Cell stem cell |
Medium |
40373768
|