PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans

FoxA transcription factors pattern gut tissue across animal phylogeny. Beyond their early patterning function, little is known about whether they control the terminal differentiation and/or function of the fully mature enteric nervous system, the intrinsic nervous system of the gut. We show here tha...

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Autores: Walker, Zion, Cao, Wen Xi, Leyva-Díaz, Eduardo, Rahman, Mayeesa, Sural, Surojit, Attner, Michelle A., Hobert, Oliver
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::07c3197b498940633c947af1640c37ab
Acceso en línea:http://hdl.handle.net/10261/430122
Access Level:acceso abierto
Palabra clave:C. elegans
Forkhead transcription factor
Enteric nervous system
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spelling PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegansWalker, ZionCao, Wen XiLeyva-Díaz, EduardoRahman, MayeesaSural, SurojitAttner, Michelle A.Hobert, OliverC. elegansForkhead transcription factorEnteric nervous systemFoxA transcription factors pattern gut tissue across animal phylogeny. Beyond their early patterning function, little is known about whether they control the terminal differentiation and/or function of the fully mature enteric nervous system, the intrinsic nervous system of the gut. We show here that the expression and function of the sole Caenorhabditis elegans FoxA homolog, PHA-4, reach beyond its previously described pioneer factor roles in patterning the foregut. Through the engineering of neuron-specific cis-regulatory alleles, Cre-mediated cell-specific knockouts, and degron-mediated, temporally controlled PHA-4/FoxA removal in postmitotic neurons, we found that PHA-4/FoxA is required not only to initiate the terminal differentiation program of foregut-associated enteric neurons but also to maintain their functional properties throughout the life of the animal. Moreover, we discovered novel sites of expression of PHA-4/FoxA in extrapharyngeal enteric neurons that innervate the hindgut (AVL and DVB), a GABAergic interneuron that controls foregut function during sleep (RIS), and a peptidergic neuron (PVT) that we implicate here in controlling defecation behavior. We show that while PHA-4/FoxA is not required for the developmental specification of AVL, DVB, RIS, and PVT, it is required to enable these neurons to control enteric functions. Taken together, PHA-4/FoxA is the only transcription factor known to date that is expressed in and required for the proper function of all distinct types of enteric neurons in a nervous system.Wethank Qi Chen for expert help in generating transgenic strains; Rudy LeDuc, Emma Grungold, and Tristian Wiles for their involvement in generating the unc-47prom::cre line; and David Raizen for providing strains. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH) Office of Research Infrastructure Programs (P40 OD010440). This work was funded in part by the NIH (R01 NS039996) and the Howard Hughes Medical Institute.Peer reviewedCold Spring Harbor Laboratory PressNational Institutes of Health (US)Howard Hughes Medical InstituteLeyva-Díaz, Eduardo [0000-0001-6750-9168]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/430122reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1101/gad.353265.125http://www.genesdev.org/cgi/doi/10.1101/gad.353265.125Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::07c3197b498940633c947af1640c37ab2026-05-22T06:33:51Z
dc.title.none.fl_str_mv PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
title PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
spellingShingle PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
Walker, Zion
C. elegans
Forkhead transcription factor
Enteric nervous system
title_short PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
title_full PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
title_fullStr PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
title_full_unstemmed PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
title_sort PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons in C. elegans
dc.creator.none.fl_str_mv Walker, Zion
Cao, Wen Xi
Leyva-Díaz, Eduardo
Rahman, Mayeesa
Sural, Surojit
Attner, Michelle A.
Hobert, Oliver
author Walker, Zion
author_facet Walker, Zion
Cao, Wen Xi
Leyva-Díaz, Eduardo
Rahman, Mayeesa
Sural, Surojit
Attner, Michelle A.
Hobert, Oliver
author_role author
author2 Cao, Wen Xi
Leyva-Díaz, Eduardo
Rahman, Mayeesa
Sural, Surojit
Attner, Michelle A.
Hobert, Oliver
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv National Institutes of Health (US)
Howard Hughes Medical Institute
Leyva-Díaz, Eduardo [0000-0001-6750-9168]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv C. elegans
Forkhead transcription factor
Enteric nervous system
topic C. elegans
Forkhead transcription factor
Enteric nervous system
description FoxA transcription factors pattern gut tissue across animal phylogeny. Beyond their early patterning function, little is known about whether they control the terminal differentiation and/or function of the fully mature enteric nervous system, the intrinsic nervous system of the gut. We show here that the expression and function of the sole Caenorhabditis elegans FoxA homolog, PHA-4, reach beyond its previously described pioneer factor roles in patterning the foregut. Through the engineering of neuron-specific cis-regulatory alleles, Cre-mediated cell-specific knockouts, and degron-mediated, temporally controlled PHA-4/FoxA removal in postmitotic neurons, we found that PHA-4/FoxA is required not only to initiate the terminal differentiation program of foregut-associated enteric neurons but also to maintain their functional properties throughout the life of the animal. Moreover, we discovered novel sites of expression of PHA-4/FoxA in extrapharyngeal enteric neurons that innervate the hindgut (AVL and DVB), a GABAergic interneuron that controls foregut function during sleep (RIS), and a peptidergic neuron (PVT) that we implicate here in controlling defecation behavior. We show that while PHA-4/FoxA is not required for the developmental specification of AVL, DVB, RIS, and PVT, it is required to enable these neurons to control enteric functions. Taken together, PHA-4/FoxA is the only transcription factor known to date that is expressed in and required for the proper function of all distinct types of enteric neurons in a nervous system.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/430122
url http://hdl.handle.net/10261/430122
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1101/gad.353265.125
http://www.genesdev.org/cgi/doi/10.1101/gad.353265.125
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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