SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects

Abstract Cleft lip and/or palate (CL/P) are common anomalies occurring in 1/800 live-births. Pathogenic SPECC1L variants have been identified in patients with CL/P, which signifies a primary role for SPECC1L in craniofacial development. Specc1l mutant mouse embryos exhibit delayed palatal shelf elev...

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Autores principales:	Jeremy P. Goering, Dona G. Isai, Everett G. Hall, Nathan R. Wilson, Edina Kosa, Luke W. Wenger, Zaid Umar, Abdul Yousaf, Andras Czirok, Irfan Saadi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2fdb4bc38df495ea530b8f2277c226b
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spelling	oai:doaj.org-article:f2fdb4bc38df495ea530b8f2277c226b2021-12-02T15:23:03ZSPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects10.1038/s41598-021-81123-92045-2322https://doaj.org/article/f2fdb4bc38df495ea530b8f2277c226b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81123-9https://doaj.org/toc/2045-2322Abstract Cleft lip and/or palate (CL/P) are common anomalies occurring in 1/800 live-births. Pathogenic SPECC1L variants have been identified in patients with CL/P, which signifies a primary role for SPECC1L in craniofacial development. Specc1l mutant mouse embryos exhibit delayed palatal shelf elevation accompanied by epithelial defects. We now posit that the process of palate elevation is itself abnormal in Specc1l mutants, due to defective remodeling of palatal mesenchyme. To characterize the underlying cellular defect, we studied the movement of primary mouse embryonic palatal mesenchyme (MEPM) cells using live-imaging of wound-repair assays. SPECC1L-deficient MEPM cells exhibited delayed wound-repair, however, reduced cell speed only partially accounted for this delay. Interestingly, mutant MEPM cells were also defective in coordinated cell movement. Therefore, we used open-field 2D cultures of wildtype MEPM cells to show that they indeed formed cell streams at high density, which is an important attribute of collective movement. Furthermore, activation of the PI3K-AKT pathway rescued both cell speed and guidance defects in Specc1l mutant MEPM cells. Thus, we show that live-imaging of primary MEPM cells can be used to assess mesenchymal remodeling defects during palatal shelf elevation, and identify a novel role for SPECC1L in collective movement through modulation of PI3K-AKT signaling.Jeremy P. GoeringDona G. IsaiEverett G. HallNathan R. WilsonEdina KosaLuke W. WengerZaid UmarAbdul YousafAndras CzirokIrfan SaadiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeremy P. Goering Dona G. Isai Everett G. Hall Nathan R. Wilson Edina Kosa Luke W. Wenger Zaid Umar Abdul Yousaf Andras Czirok Irfan Saadi SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
description	Abstract Cleft lip and/or palate (CL/P) are common anomalies occurring in 1/800 live-births. Pathogenic SPECC1L variants have been identified in patients with CL/P, which signifies a primary role for SPECC1L in craniofacial development. Specc1l mutant mouse embryos exhibit delayed palatal shelf elevation accompanied by epithelial defects. We now posit that the process of palate elevation is itself abnormal in Specc1l mutants, due to defective remodeling of palatal mesenchyme. To characterize the underlying cellular defect, we studied the movement of primary mouse embryonic palatal mesenchyme (MEPM) cells using live-imaging of wound-repair assays. SPECC1L-deficient MEPM cells exhibited delayed wound-repair, however, reduced cell speed only partially accounted for this delay. Interestingly, mutant MEPM cells were also defective in coordinated cell movement. Therefore, we used open-field 2D cultures of wildtype MEPM cells to show that they indeed formed cell streams at high density, which is an important attribute of collective movement. Furthermore, activation of the PI3K-AKT pathway rescued both cell speed and guidance defects in Specc1l mutant MEPM cells. Thus, we show that live-imaging of primary MEPM cells can be used to assess mesenchymal remodeling defects during palatal shelf elevation, and identify a novel role for SPECC1L in collective movement through modulation of PI3K-AKT signaling.
format	article
author	Jeremy P. Goering Dona G. Isai Everett G. Hall Nathan R. Wilson Edina Kosa Luke W. Wenger Zaid Umar Abdul Yousaf Andras Czirok Irfan Saadi
author_facet	Jeremy P. Goering Dona G. Isai Everett G. Hall Nathan R. Wilson Edina Kosa Luke W. Wenger Zaid Umar Abdul Yousaf Andras Czirok Irfan Saadi
author_sort	Jeremy P. Goering
title	SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
title_short	SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
title_full	SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
title_fullStr	SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
title_full_unstemmed	SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
title_sort	specc1l-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f2fdb4bc38df495ea530b8f2277c226b
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SPECC1L-deficient primary mouse embryonic palatal mesenchyme cells show speed and directionality defects

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