Dataset Information

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human.

ABSTRACT: TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analyzed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional knockout mouse model showed that ENS formation did not require TALPID3, but was dependent on correct environmental cues. Surprisingly, the lack of TALPID3 in enteric neural crest cells (ENCC) affected smooth muscle and epithelial development in a non-cell-autonomous manner. Analysis of human gut fetal tissues with a KIAA0586 mutation showed strikingly similar findings compared to the animal models demonstrating conservation of TALPID3 and its necessary role in human GI tract development and patterning.

SUBMITTER: Delalande JM

PROVIDER: S-EPMC8733242 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human.

Delalande Jean Marie JM Nagy Nandor N McCann Conor J CJ Natarajan Dipa D Cooper Julie E JE Carreno Gabriela G Dora David D Campbell Alison A Laurent Nicole N Kemos Polychronis P Thomas Sophie S Alby Caroline C Attié-Bitach Tania T Lyonnet Stanislas S Logan Malcolm P MP Goldstein Allan M AM Davey Megan G MG Hofstra Robert M W RMW Thapar Nikhil N Burns Alan J AJ

Frontiers in molecular neuroscience 20211223

TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analyzed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gu ...[more]

PMID: 35002618

Similar Datasets

Project description:Joubert syndrome (JS) is a ciliopathy associated with mutations in numerous genes encoding cilia components. TALPID3 encoded by KIAA0856 in man (2700049A03Rik in mouse) is a centrosomal protein essential for the assembly of primary cilia. Mutations in KIAA0856 have been recently identified in JS patients. Herein, we describe a novel mouse JS model with a conditional deletion of the conserved exons 11-12 of Talpid3 in the central nervous system which recapitulates the complete cerebellar phenotype seen in JS. Talpid3 mutant mice exhibit key hallmarks of JS including progressive ataxia, severely hypoplastic cerebellar hemispheres and vermis, together with abnormal decussation of the superior cerebellar peduncles. The Purkinje cell layer is disorganised with abnormal dendritic arborisation. The external granule layer (EGL) is thinner, lacks primary cilia, and has a reduced level of proliferation. Furthermore, we describe novel cellular defects including ectopic clusters of mature granule neurons, and abnormal parallel fibre-derived synapses and disorientation of cells in the EGL. The defective glial scaffold results in abnormal granule cell migration which manifests as ectopic clusters of granule neurons. In addition, we show a reduction in Wnt7a expression suggesting that defects may arise not only from deficiencies in the Hedgehog (Hh) pathway but also due to the additional roles of Talpid3. The Talpid3 conditional knockout mouse is a novel JS model which fully recapitulates the JS cerebellar phenotype. These findings reveal a role for Talpid3 in granule precursor cell migration in the cerebellum (either direct or indirect) which together with defective Hh signalling underlies the JS phenotype. Our findings also illustrate the utility of creating conditional mouse models to assist in unravelling the molecular and cellular mechanisms underlying JS. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Dataset Information

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human.

Publications

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets