Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons

Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation. In this study, we identified Cadherin-12 (CDH12), which encodes a type II classical cadherin, as a gene that promotes neurite outgro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Beibei Guo, Mengwei Qi, Shuai Huang, Run Zhuo, Wenxue Zhang, Yufang Zhang, Man Xu, Mei Liu, Tuchen Guan, Yan Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Cadherin-12 neurite outgrowth cAMP/PKA pathway Rac1/Cdc42 NgAgo Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fc600c56d58645d1b41222c3d193d776
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fc600c56d58645d1b41222c3d193d776
record_format	dspace
spelling	oai:doaj.org-article:fc600c56d58645d1b41222c3d193d7762021-11-08T06:10:53ZCadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons2296-634X10.3389/fcell.2021.768970https://doaj.org/article/fc600c56d58645d1b41222c3d193d7762021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.768970/fullhttps://doaj.org/toc/2296-634XCadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation. In this study, we identified Cadherin-12 (CDH12), which encodes a type II classical cadherin, as a gene that promotes neurite outgrowth in an in vitro model of neurons with differentiated intrinsic growth ability. First, the effects of CDH12 on neurons were evaluated via RNA interference, and the results indicated that the knockdown of CDH12 expression restrained the axon extension of E18 neurons. The transcriptome profile of neurons with or without siCDH12 treatment revealed a set of pathways positively correlated with the effect of CDH12 on neurite outgrowth. We further revealed that CDH12 affected Rac1/Cdc42 phosphorylation in a PKA-dependent manner after testing using H-89 and 8-Bromo-cAMP sodium salt. Moreover, we investigated the expression of CDH12 in the brain, spinal cord, and dorsal root ganglia (DRG) during development using immunofluorescence staining. After that, we explored the effects of CDH12 on neurite outgrowth in vivo. A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system, and the vital role of CDH12 in peripheral neurogenesis was determined. In summary, our study is the first to report the effect of CDH12 on axonal extension in vitro and in vivo, and we provide a preliminary explanation for this mechanism.Beibei GuoMengwei QiShuai HuangRun ZhuoWenxue ZhangYufang ZhangMan XuMei LiuTuchen GuanYan LiuFrontiers Media S.A.articleCadherin-12neurite outgrowthcAMP/PKA pathwayRac1/Cdc42NgAgoBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cadherin-12 neurite outgrowth cAMP/PKA pathway Rac1/Cdc42 NgAgo Biology (General) QH301-705.5
spellingShingle	Cadherin-12 neurite outgrowth cAMP/PKA pathway Rac1/Cdc42 NgAgo Biology (General) QH301-705.5 Beibei Guo Mengwei Qi Shuai Huang Run Zhuo Wenxue Zhang Yufang Zhang Man Xu Mei Liu Tuchen Guan Yan Liu Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons
description	Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation. In this study, we identified Cadherin-12 (CDH12), which encodes a type II classical cadherin, as a gene that promotes neurite outgrowth in an in vitro model of neurons with differentiated intrinsic growth ability. First, the effects of CDH12 on neurons were evaluated via RNA interference, and the results indicated that the knockdown of CDH12 expression restrained the axon extension of E18 neurons. The transcriptome profile of neurons with or without siCDH12 treatment revealed a set of pathways positively correlated with the effect of CDH12 on neurite outgrowth. We further revealed that CDH12 affected Rac1/Cdc42 phosphorylation in a PKA-dependent manner after testing using H-89 and 8-Bromo-cAMP sodium salt. Moreover, we investigated the expression of CDH12 in the brain, spinal cord, and dorsal root ganglia (DRG) during development using immunofluorescence staining. After that, we explored the effects of CDH12 on neurite outgrowth in vivo. A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system, and the vital role of CDH12 in peripheral neurogenesis was determined. In summary, our study is the first to report the effect of CDH12 on axonal extension in vitro and in vivo, and we provide a preliminary explanation for this mechanism.
format	article
author	Beibei Guo Mengwei Qi Shuai Huang Run Zhuo Wenxue Zhang Yufang Zhang Man Xu Mei Liu Tuchen Guan Yan Liu
author_facet	Beibei Guo Mengwei Qi Shuai Huang Run Zhuo Wenxue Zhang Yufang Zhang Man Xu Mei Liu Tuchen Guan Yan Liu
author_sort	Beibei Guo
title	Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons
title_short	Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons
title_full	Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons
title_fullStr	Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons
title_full_unstemmed	Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons
title_sort	cadherin-12 regulates neurite outgrowth through the pka/rac1/cdc42 pathway in cortical neurons
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/fc600c56d58645d1b41222c3d193d776
work_keys_str_mv	AT beibeiguo cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT mengweiqi cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT shuaihuang cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT runzhuo cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT wenxuezhang cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT yufangzhang cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT manxu cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT meiliu cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT tuchenguan cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons AT yanliu cadherin12regulatesneuriteoutgrowththroughthepkarac1cdc42pathwayincorticalneurons
_version_	1718442965656928256

Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons

Ejemplares similares