ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos

ERBB family members and their ligands play an essential role in embryonic heart development and adult heart physiology. Among them, ERBB3 is a binding partner of ERBB2; the ERBB2/3 complex mediates downstream signaling for cell proliferation. ERBB3 has seven consensus binding sites to the p85 regula...

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Autores principales:	Kyoungmi Kim, Daekee Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e43d7a990f54efdb0bedb02464eb669
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spelling	oai:doaj.org-article:7e43d7a990f54efdb0bedb02464eb6692021-11-04T06:49:30ZERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos1932-6203https://doaj.org/article/7e43d7a990f54efdb0bedb02464eb6692021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555822/?tool=EBIhttps://doaj.org/toc/1932-6203ERBB family members and their ligands play an essential role in embryonic heart development and adult heart physiology. Among them, ERBB3 is a binding partner of ERBB2; the ERBB2/3 complex mediates downstream signaling for cell proliferation. ERBB3 has seven consensus binding sites to the p85 regulatory subunit of PI3K, which activates the downstream AKT pathway, leading to the proliferation of various cells. This study generated a human ERBB3 knock-in mouse expressing a mutant ERBB3 whose seven YXXM p85 binding sites were replaced with YXXA. Erbb3 knock-in embryos exhibited lethality between E12.5 to E13.5, and showed a decrease in mesenchymal cell numbers and density in AV cushions. We determined that the proliferation of mesenchymal cells in the atrioventricular (AV) cushion in Erbb3 knock-in mutant embryos was temporarily reduced due to the decrease of AKT and ERK1/2 phosphorylation. Overall, our results suggest that AKT/ERK activation by the ERBB3-dependent PI3K signaling is crucial for AV cushion morphogenesis during embryonic heart development.Kyoungmi KimDaekee LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyoungmi Kim Daekee Lee ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos
description	ERBB family members and their ligands play an essential role in embryonic heart development and adult heart physiology. Among them, ERBB3 is a binding partner of ERBB2; the ERBB2/3 complex mediates downstream signaling for cell proliferation. ERBB3 has seven consensus binding sites to the p85 regulatory subunit of PI3K, which activates the downstream AKT pathway, leading to the proliferation of various cells. This study generated a human ERBB3 knock-in mouse expressing a mutant ERBB3 whose seven YXXM p85 binding sites were replaced with YXXA. Erbb3 knock-in embryos exhibited lethality between E12.5 to E13.5, and showed a decrease in mesenchymal cell numbers and density in AV cushions. We determined that the proliferation of mesenchymal cells in the atrioventricular (AV) cushion in Erbb3 knock-in mutant embryos was temporarily reduced due to the decrease of AKT and ERK1/2 phosphorylation. Overall, our results suggest that AKT/ERK activation by the ERBB3-dependent PI3K signaling is crucial for AV cushion morphogenesis during embryonic heart development.
format	article
author	Kyoungmi Kim Daekee Lee
author_facet	Kyoungmi Kim Daekee Lee
author_sort	Kyoungmi Kim
title	ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos
title_short	ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos
title_full	ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos
title_fullStr	ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos
title_full_unstemmed	ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos
title_sort	erbb3-dependent akt and erk pathways are essential for atrioventricular cushion development in mouse embryos
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7e43d7a990f54efdb0bedb02464eb669
work_keys_str_mv	AT kyoungmikim erbb3dependentaktanderkpathwaysareessentialforatrioventricularcushiondevelopmentinmouseembryos AT daekeelee erbb3dependentaktanderkpathwaysareessentialforatrioventricularcushiondevelopmentinmouseembryos
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ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos

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