Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/cells11081295 http://hdl.handle.net/11449/239883 |
Resumo: | Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor α1-GFRα1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in mammalian testes. In nonmammalian species, Gdnf and Gfrα1 orthologs have been found but their functions remain poorly investigated in the testes. Considering this background, this study aimed to understand the roles of the Gdnf-Gfrα1 signaling pathway in zebrafish testes by combining in vivo, in silico and ex vivo approaches. Our analysis showed that zebrafish exhibit two paralogs for Gndf (gdnfa and gdnfb) and its receptor, Gfrα1 (gfrα1a and gfrα1b), in accordance with a teleost-specific third round of whole genome duplication. Expression analysis further revealed that both ligands and receptors were expressed in zebrafish adult testes. Subsequently, we demonstrated that gdnfa is expressed in the germ cells, while Gfrα1a/Gfrα1b was detected in early spermatogonia (mainly in types Aund and Adiff) and Sertoli cells. Functional ex vivo analysis showed that Gdnf promoted the creation of new available niches by stimulating the proliferation of both type Aund spermatogonia and their surrounding Sertoli cells but without changing pou5f3 mRNA levels. Strikingly, Gdnf also inhibited late spermatogonial differentiation, as shown by the decrease in type B spermatogonia and down-regulation of dazl in a co-treatment with Fsh. Altogether, our data revealed that a germ cell-derived factor is involved in maintaining germ cell stemness through the creation of new available niches, supporting the development of spermatogonial cysts and inhibiting late spermatogonial differentiation in autocrine-and paracrine-dependent manners. |
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Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent MannersGdnfGfrα1spermatogenesisspermatogonial stem cellzebrafishGlial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor α1-GFRα1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in mammalian testes. In nonmammalian species, Gdnf and Gfrα1 orthologs have been found but their functions remain poorly investigated in the testes. Considering this background, this study aimed to understand the roles of the Gdnf-Gfrα1 signaling pathway in zebrafish testes by combining in vivo, in silico and ex vivo approaches. Our analysis showed that zebrafish exhibit two paralogs for Gndf (gdnfa and gdnfb) and its receptor, Gfrα1 (gfrα1a and gfrα1b), in accordance with a teleost-specific third round of whole genome duplication. Expression analysis further revealed that both ligands and receptors were expressed in zebrafish adult testes. Subsequently, we demonstrated that gdnfa is expressed in the germ cells, while Gfrα1a/Gfrα1b was detected in early spermatogonia (mainly in types Aund and Adiff) and Sertoli cells. Functional ex vivo analysis showed that Gdnf promoted the creation of new available niches by stimulating the proliferation of both type Aund spermatogonia and their surrounding Sertoli cells but without changing pou5f3 mRNA levels. Strikingly, Gdnf also inhibited late spermatogonial differentiation, as shown by the decrease in type B spermatogonia and down-regulation of dazl in a co-treatment with Fsh. Altogether, our data revealed that a germ cell-derived factor is involved in maintaining germ cell stemness through the creation of new available niches, supporting the development of spermatogonial cysts and inhibiting late spermatogonial differentiation in autocrine-and paracrine-dependent manners.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Reproductive and Molecular Biology Group Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP)Biological Research Laboratory Goiano Federal Institution—Urata Campus, Rodovia Geraldo Silva Nascimento, 2.5 km, GOKey Lab of Sustainable Development of Marine Fisheries Ministry of Agriculture and Rural Affairs Yellow Sea Fisheries Research Institute Chinese Academy of Fishery SciencesLaboratory for Marine Fisheries Science and Food Production Processes Qingdao National Laboratory for Marine Science and TechnologyReproductive and Molecular Biology Group Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP)CAPES: 001FAPESP: 2014/07620–7FAPESP: 2016/12101-4FAPESP: 2017/08274-3FAPESP: 2020/03569-8CNPq: 305808/2020-6CNPq: 307743/2018–7Universidade Estadual Paulista (UNESP)Goiano Federal Institution—Urata CampusChinese Academy of Fishery SciencesQingdao National Laboratory for Marine Science and TechnologyDoretto, Lucas B. [UNESP]Butzge, Arno J. [UNESP]Nakajima, Rafael T. [UNESP]Martinez, Emanuel R. M. [UNESP]Souza, Beatriz Marques de[UNESP]Rodrigues, Maira da Silva [UNESP]Rosa, Ivana F. [UNESP]Ricci, Juliana M. B. [UNESP]Tovo-Neto, Aldo [UNESP]Costa, Daniel F. [UNESP]Malafaia, Guilherme [UNESP]Shao, ChangweiNóbrega, Rafael H. [UNESP]2023-03-01T19:51:46Z2023-03-01T19:51:46Z2022-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/cells11081295Cells, v. 11, n. 8, 2022.2073-4409http://hdl.handle.net/11449/23988310.3390/cells110812952-s2.0-85128209646Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCellsinfo:eu-repo/semantics/openAccess2023-03-01T19:51:46Zoai:repositorio.unesp.br:11449/239883Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T13:42:35.686630Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners |
title |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners |
spellingShingle |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners Doretto, Lucas B. [UNESP] Gdnf Gfrα1 spermatogenesis spermatogonial stem cell zebrafish |
title_short |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners |
title_full |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners |
title_fullStr |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners |
title_full_unstemmed |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners |
title_sort |
Gdnf Acts as a Germ Cell-Derived Growth Factor and Regulates the Zebrafish Germ Stem Cell Niche in Autocrine-and Paracrine-Dependent Manners |
author |
Doretto, Lucas B. [UNESP] |
author_facet |
Doretto, Lucas B. [UNESP] Butzge, Arno J. [UNESP] Nakajima, Rafael T. [UNESP] Martinez, Emanuel R. M. [UNESP] Souza, Beatriz Marques de[UNESP] Rodrigues, Maira da Silva [UNESP] Rosa, Ivana F. [UNESP] Ricci, Juliana M. B. [UNESP] Tovo-Neto, Aldo [UNESP] Costa, Daniel F. [UNESP] Malafaia, Guilherme [UNESP] Shao, Changwei Nóbrega, Rafael H. [UNESP] |
author_role |
author |
author2 |
Butzge, Arno J. [UNESP] Nakajima, Rafael T. [UNESP] Martinez, Emanuel R. M. [UNESP] Souza, Beatriz Marques de[UNESP] Rodrigues, Maira da Silva [UNESP] Rosa, Ivana F. [UNESP] Ricci, Juliana M. B. [UNESP] Tovo-Neto, Aldo [UNESP] Costa, Daniel F. [UNESP] Malafaia, Guilherme [UNESP] Shao, Changwei Nóbrega, Rafael H. [UNESP] |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Goiano Federal Institution—Urata Campus Chinese Academy of Fishery Sciences Qingdao National Laboratory for Marine Science and Technology |
dc.contributor.author.fl_str_mv |
Doretto, Lucas B. [UNESP] Butzge, Arno J. [UNESP] Nakajima, Rafael T. [UNESP] Martinez, Emanuel R. M. [UNESP] Souza, Beatriz Marques de[UNESP] Rodrigues, Maira da Silva [UNESP] Rosa, Ivana F. [UNESP] Ricci, Juliana M. B. [UNESP] Tovo-Neto, Aldo [UNESP] Costa, Daniel F. [UNESP] Malafaia, Guilherme [UNESP] Shao, Changwei Nóbrega, Rafael H. [UNESP] |
dc.subject.por.fl_str_mv |
Gdnf Gfrα1 spermatogenesis spermatogonial stem cell zebrafish |
topic |
Gdnf Gfrα1 spermatogenesis spermatogonial stem cell zebrafish |
description |
Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor α1-GFRα1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in mammalian testes. In nonmammalian species, Gdnf and Gfrα1 orthologs have been found but their functions remain poorly investigated in the testes. Considering this background, this study aimed to understand the roles of the Gdnf-Gfrα1 signaling pathway in zebrafish testes by combining in vivo, in silico and ex vivo approaches. Our analysis showed that zebrafish exhibit two paralogs for Gndf (gdnfa and gdnfb) and its receptor, Gfrα1 (gfrα1a and gfrα1b), in accordance with a teleost-specific third round of whole genome duplication. Expression analysis further revealed that both ligands and receptors were expressed in zebrafish adult testes. Subsequently, we demonstrated that gdnfa is expressed in the germ cells, while Gfrα1a/Gfrα1b was detected in early spermatogonia (mainly in types Aund and Adiff) and Sertoli cells. Functional ex vivo analysis showed that Gdnf promoted the creation of new available niches by stimulating the proliferation of both type Aund spermatogonia and their surrounding Sertoli cells but without changing pou5f3 mRNA levels. Strikingly, Gdnf also inhibited late spermatogonial differentiation, as shown by the decrease in type B spermatogonia and down-regulation of dazl in a co-treatment with Fsh. Altogether, our data revealed that a germ cell-derived factor is involved in maintaining germ cell stemness through the creation of new available niches, supporting the development of spermatogonial cysts and inhibiting late spermatogonial differentiation in autocrine-and paracrine-dependent manners. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-04-01 2023-03-01T19:51:46Z 2023-03-01T19:51:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/cells11081295 Cells, v. 11, n. 8, 2022. 2073-4409 http://hdl.handle.net/11449/239883 10.3390/cells11081295 2-s2.0-85128209646 |
url |
http://dx.doi.org/10.3390/cells11081295 http://hdl.handle.net/11449/239883 |
identifier_str_mv |
Cells, v. 11, n. 8, 2022. 2073-4409 10.3390/cells11081295 2-s2.0-85128209646 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cells |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128268910460928 |