Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development

Abstract The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key roles in development of the cardiac outflow tract (OFT) for establishment of completely separated pulmonary and systemic circulations in vertebrates. A neurovascular guiding factor, Semaphorin 3c (Sema3c), is r...

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Autores principales:	Kazuki Kodo, Shinsuke Shibata, Sachiko Miyagawa-Tomita, Sang-Ging Ong, Hiroshi Takahashi, Tsutomu Kume, Hideyuki Okano, Rumiko Matsuoka, Hiroyuki Yamagishi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13a01baded6f471487968b40ed5721d1
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spelling	oai:doaj.org-article:13a01baded6f471487968b40ed5721d12021-12-02T15:05:25ZRegulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development10.1038/s41598-017-06964-92045-2322https://doaj.org/article/13a01baded6f471487968b40ed5721d12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06964-9https://doaj.org/toc/2045-2322Abstract The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key roles in development of the cardiac outflow tract (OFT) for establishment of completely separated pulmonary and systemic circulations in vertebrates. A neurovascular guiding factor, Semaphorin 3c (Sema3c), is required for the development of the OFT, however, its regulation of the interaction between cNCCs and SHF remains to be determined. Here, we show that a Sema3c is a candidate that mediates interaction between cNCCs and the SHF during development of the OFT. Foxc1/c2 directly activates the transcription of Sema3c in the OFT, whereas, a hypomorph of Tbx1, a key SHF transcription factor, resulted in the ectopic expression of Sema3c in the pharyngeal arch region. Fgf8, a downstream secreted factor of Tbx1, inhibited the expression of Sema3c in cNCCs via activation of ERK1/2 signaling. Blocking of FGF8 caused ectopic expression of SEMA3C and a migration defect of cNCCs, resulting in abnormal chick pharyngeal arch development. These results suggest that proper spatio-temporal expression of Sema3c, regulated positively by Foxc1/c2 and negatively by the Tbx1-Fgf8 cascade, respectively, is essential for the interaction between cNCCs and the SHF that correctly navigates cNCCs towards the OFT, composed of SHF-derived cells.Kazuki KodoShinsuke ShibataSachiko Miyagawa-TomitaSang-Ging OngHiroshi TakahashiTsutomu KumeHideyuki OkanoRumiko MatsuokaHiroyuki YamagishiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazuki Kodo Shinsuke Shibata Sachiko Miyagawa-Tomita Sang-Ging Ong Hiroshi Takahashi Tsutomu Kume Hideyuki Okano Rumiko Matsuoka Hiroyuki Yamagishi Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development
description	Abstract The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key roles in development of the cardiac outflow tract (OFT) for establishment of completely separated pulmonary and systemic circulations in vertebrates. A neurovascular guiding factor, Semaphorin 3c (Sema3c), is required for the development of the OFT, however, its regulation of the interaction between cNCCs and SHF remains to be determined. Here, we show that a Sema3c is a candidate that mediates interaction between cNCCs and the SHF during development of the OFT. Foxc1/c2 directly activates the transcription of Sema3c in the OFT, whereas, a hypomorph of Tbx1, a key SHF transcription factor, resulted in the ectopic expression of Sema3c in the pharyngeal arch region. Fgf8, a downstream secreted factor of Tbx1, inhibited the expression of Sema3c in cNCCs via activation of ERK1/2 signaling. Blocking of FGF8 caused ectopic expression of SEMA3C and a migration defect of cNCCs, resulting in abnormal chick pharyngeal arch development. These results suggest that proper spatio-temporal expression of Sema3c, regulated positively by Foxc1/c2 and negatively by the Tbx1-Fgf8 cascade, respectively, is essential for the interaction between cNCCs and the SHF that correctly navigates cNCCs towards the OFT, composed of SHF-derived cells.
format	article
author	Kazuki Kodo Shinsuke Shibata Sachiko Miyagawa-Tomita Sang-Ging Ong Hiroshi Takahashi Tsutomu Kume Hideyuki Okano Rumiko Matsuoka Hiroyuki Yamagishi
author_facet	Kazuki Kodo Shinsuke Shibata Sachiko Miyagawa-Tomita Sang-Ging Ong Hiroshi Takahashi Tsutomu Kume Hideyuki Okano Rumiko Matsuoka Hiroyuki Yamagishi
author_sort	Kazuki Kodo
title	Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development
title_short	Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development
title_full	Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development
title_fullStr	Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development
title_full_unstemmed	Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development
title_sort	regulation of sema3c and the interaction between cardiac neural crest and second heart field during outflow tract development
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/13a01baded6f471487968b40ed5721d1
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Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development

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