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

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; Stanislas Lyonnet; Malcolm P. Logan; Allan M. Goldstein; Megan G. Davey; Robert M.W. Hofstra; Nikhil Thapar; Alan J. Burns; Alan J.  Burns

doi:10.3389/fnmol.2021.757646

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

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, Stanislas Lyonnet, Malcolm P. Logan, Allan M. Goldstein, Megan G. Davey, Robert M.W. Hofstra, Nikhil Thapar, Alan J. Burns^*Alan J. Burns

^*Corresponding author for this work

Clinical Genetics

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	757646
Journal	Frontiers in Molecular Neuroscience
Volume	14
DOIs	https://doi.org/10.3389/fnmol.2021.757646
Publication status	Published - 23 Dec 2021

Bibliographical note

Funding Information:
This article is dedicated to the memory of RH. We would like to thank Dagan Jenkins for the IFT88 antibody, Mark Turmaine for assistance with SEM, Kevin Lee and Erwin Pauws for assistance with cartilage and bone staining as well as help with the phenotype analysis. We also thank Jan Soetaert and Bel?n Mart?n-Mart?n for help with microscopy. MD and the TALPID3 flock are supported by an Institutional Strategic Grant (ISP) to The Roslin Institute from the BBSRC. NN was supported by a Bolyai Fellowship and Hungarian Science Foundation NKFI grant (124740). CM was supported by Guts UK (Derek Butler Fellowship). We are grateful to the French Society of Fetal Pathology (SoFFoet) for participating in the study. We acknowledge the NIHR Great Ormond Street Hospital Biomedical Research Centre which supports all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Publisher Copyright:
Copyright © 2021 Delalande, Nagy, McCann, Natarajan, Cooper, Carreno, Dora, Campbell, Laurent, Kemos, Thomas, Alby, Attié-Bitach, Lyonnet, Logan, Goldstein, Davey, Hofstra, Thapar and Burns.

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TALPID3,KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and HumanFinal published version, 6.87 MBLicence: CC BY

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Delalande, J. M., Nagy, N., McCann, C. J., Natarajan, D., Cooper, J. E., Carreno, G., Dora, D., Campbell, A., Laurent, N., Kemos, P., Thomas, S., Alby, C., Attié-Bitach, T., Lyonnet, S., Logan, M. P., Goldstein, A. M., Davey, M. G., Hofstra, R. M. W., Thapar, N., ... Burns, A. J. (2021). TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human. Frontiers in Molecular Neuroscience, 14, [757646]. https://doi.org/10.3389/fnmol.2021.757646

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title = "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.",

author = "Delalande, {Jean Marie} and Nandor Nagy and McCann, {Conor J.} and Dipa Natarajan and Cooper, {Julie E.} and Gabriela Carreno and David Dora and Alison Campbell and Nicole Laurent and Polychronis Kemos and Sophie Thomas and Caroline Alby and Tania Atti{\'e}-Bitach and Stanislas Lyonnet and Logan, {Malcolm P.} and Goldstein, {Allan M.} and Davey, {Megan G.} and Hofstra, {Robert M.W.} and Nikhil Thapar and Burns, {Alan J.} and Burns, {Alan J.}",

note = "Funding Information: This article is dedicated to the memory of RH. We would like to thank Dagan Jenkins for the IFT88 antibody, Mark Turmaine for assistance with SEM, Kevin Lee and Erwin Pauws for assistance with cartilage and bone staining as well as help with the phenotype analysis. We also thank Jan Soetaert and Bel?n Mart?n-Mart?n for help with microscopy. MD and the TALPID3 flock are supported by an Institutional Strategic Grant (ISP) to The Roslin Institute from the BBSRC. NN was supported by a Bolyai Fellowship and Hungarian Science Foundation NKFI grant (124740). CM was supported by Guts UK (Derek Butler Fellowship). We are grateful to the French Society of Fetal Pathology (SoFFoet) for participating in the study. We acknowledge the NIHR Great Ormond Street Hospital Biomedical Research Centre which supports all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Publisher Copyright: Copyright {\textcopyright} 2021 Delalande, Nagy, McCann, Natarajan, Cooper, Carreno, Dora, Campbell, Laurent, Kemos, Thomas, Alby, Atti{\'e}-Bitach, Lyonnet, Logan, Goldstein, Davey, Hofstra, Thapar and Burns.",

year = "2021",

month = dec,

day = "23",

doi = "10.3389/fnmol.2021.757646",

language = "English",

volume = "14",

journal = "Frontiers in Molecular Neuroscience",

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Delalande, JM, Nagy, N, McCann, CJ, Natarajan, D, Cooper, JE, Carreno, G, Dora, D, Campbell, A, Laurent, N, Kemos, P, Thomas, S, Alby, C, Attié-Bitach, T, Lyonnet, S, Logan, MP, Goldstein, AM, Davey, MG, Hofstra, RMW, Thapar, N, Burns, AJ & Burns, AJ 2021, 'TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human', Frontiers in Molecular Neuroscience, vol. 14, 757646. https://doi.org/10.3389/fnmol.2021.757646

TY - JOUR

T1 - TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human

AU - Delalande, Jean Marie

AU - Nagy, Nandor

AU - McCann, Conor J.

AU - Natarajan, Dipa

AU - Cooper, Julie E.

AU - Carreno, Gabriela

AU - Dora, David

AU - Campbell, Alison

AU - Laurent, Nicole

AU - Kemos, Polychronis

AU - Thomas, Sophie

AU - Alby, Caroline

AU - Attié-Bitach, Tania

AU - Lyonnet, Stanislas

AU - Logan, Malcolm P.

AU - Goldstein, Allan M.

AU - Davey, Megan G.

AU - Hofstra, Robert M.W.

AU - Thapar, Nikhil

AU - Burns, Alan J.

N1 - Funding Information: This article is dedicated to the memory of RH. We would like to thank Dagan Jenkins for the IFT88 antibody, Mark Turmaine for assistance with SEM, Kevin Lee and Erwin Pauws for assistance with cartilage and bone staining as well as help with the phenotype analysis. We also thank Jan Soetaert and Bel?n Mart?n-Mart?n for help with microscopy. MD and the TALPID3 flock are supported by an Institutional Strategic Grant (ISP) to The Roslin Institute from the BBSRC. NN was supported by a Bolyai Fellowship and Hungarian Science Foundation NKFI grant (124740). CM was supported by Guts UK (Derek Butler Fellowship). We are grateful to the French Society of Fetal Pathology (SoFFoet) for participating in the study. We acknowledge the NIHR Great Ormond Street Hospital Biomedical Research Centre which supports all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Publisher Copyright: Copyright © 2021 Delalande, Nagy, McCann, Natarajan, Cooper, Carreno, Dora, Campbell, Laurent, Kemos, Thomas, Alby, Attié-Bitach, Lyonnet, Logan, Goldstein, Davey, Hofstra, Thapar and Burns.

PY - 2021/12/23

Y1 - 2021/12/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85122351876&partnerID=8YFLogxK

U2 - 10.3389/fnmol.2021.757646

DO - 10.3389/fnmol.2021.757646

M3 - Article

AN - SCOPUS:85122351876

SN - 1662-5099

VL - 14

JO - Frontiers in Molecular Neuroscience

JF - Frontiers in Molecular Neuroscience

M1 - 757646

ER -

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

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