Frontiers in Molecular Neuroscience (Dec 2021)
TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human
- Jean Marie Delalande,
- Jean Marie Delalande,
- Nandor Nagy,
- Conor J. McCann,
- Dipa Natarajan,
- Julie E. Cooper,
- Gabriela Carreno,
- David Dora,
- Alison Campbell,
- Nicole Laurent,
- Polychronis Kemos,
- Sophie Thomas,
- Caroline Alby,
- Tania Attié-Bitach,
- Tania Attié-Bitach,
- Tania Attié-Bitach,
- Stanislas Lyonnet,
- Stanislas Lyonnet,
- Stanislas Lyonnet,
- Malcolm P. Logan,
- Allan M. Goldstein,
- Megan G. Davey,
- Robert M. W. Hofstra,
- Nikhil Thapar,
- Nikhil Thapar,
- Alan J. Burns,
- Alan J. Burns,
- Alan J. Burns
Affiliations
- Jean Marie Delalande
- Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Jean Marie Delalande
- Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- Nandor Nagy
- Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
- Conor J. McCann
- Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- Dipa Natarajan
- Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- Julie E. Cooper
- Developmental Biology and Cancer Program, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- Gabriela Carreno
- Developmental Biology and Cancer Program, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- David Dora
- Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
- Alison Campbell
- Department of Paediatric Surgery, Christchurch Hospital, Christchurch, New Zealand
- Nicole Laurent
- Génétique et Anomalies du Développement, Université de Bourgogne, Service d’Anatomie Pathologique, Dijon, France
- Polychronis Kemos
- Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Sophie Thomas
- Laboratory of Embryology and Genetics of Congenital Malformations, INSERM UMR 1163 Institut Imagine, Paris, France
- Caroline Alby
- Department of Genetics, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France
- Tania Attié-Bitach
- Laboratory of Embryology and Genetics of Congenital Malformations, INSERM UMR 1163 Institut Imagine, Paris, France
- Tania Attié-Bitach
- Department of Genetics, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France
- Tania Attié-Bitach
- Paris Descartes, Sorbonne Paris Cité, Paris, France
- Stanislas Lyonnet
- Laboratory of Embryology and Genetics of Congenital Malformations, INSERM UMR 1163 Institut Imagine, Paris, France
- Stanislas Lyonnet
- Department of Genetics, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France
- Stanislas Lyonnet
- Paris Descartes, Sorbonne Paris Cité, Paris, France
- Malcolm P. Logan
- 0Randall Division of Cell and Molecular Biophysics, King’s College London, London, United Kingdom
- Allan M. Goldstein
- 1Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Megan G. Davey
- 2Division of Developmental Biology, The Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom
- Robert M. W. Hofstra
- 3Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands
- Nikhil Thapar
- Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- Nikhil Thapar
- 3Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands
- Alan J. Burns
- Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
- Alan J. Burns
- 4Division of Neurogastroenterology and Motility, Department of Gastroenterology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
- Alan J. Burns
- 5Gastrointestinal Drug Discovery Unit, Takeda Pharmaceuticals International, Inc., Cambridge, MA, United States
- DOI
- https://doi.org/10.3389/fnmol.2021.757646
- Journal volume & issue
-
Vol. 14
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.
Keywords
