Universität zu Köln

Miyares, Rosa Linda, Stein, Cornelia, Renisch, Bjoern, Anderson, Jennifer Lynn, Hammerschmidt, Matthias and Farber, Steven Arthur (2013). Long-Chain Acyl-CoA Synthetase 4A Regulates Smad Activity and Dorsoventral Patterning in the Zebrafish Embryo. Dev. Cell, 27 (6). S. 635 - 648. CAMBRIDGE: CELL PRESS. ISSN 1878-1551

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Abstract

Long-chain polyunsaturated fatty acids (LC-PUFA) and their metabolites are critical players in cell biology and embryonic development. Here we show that long-chain acyl-CoA synthetase 4a (Acsl4a), an LC-PUFA activating enzyme, is essential for proper patterning of the zebrafish dorsoventral axis. Loss of Acsl4a results in dorsalized embryos due to attenuated bone morphogenetic protein (Bmp) signaling. We demonstrate that Acsl4a modulates the activity of Smad transcription factors, the downstream mediators of Bmp signaling. Acsl4a promotes the inhibition of p38 mitogen-activated protein kinase and the Akt-mediated inhibition of glycogen synthase kinase 3, critical inhibitors of Smad activity. Consequently, introduction of a constitutively active Akt can rescue the dorsalized phenotype of Acsl4a-deficient embryos. Our results reveal a critical role for Acsl4a in modulating Bmp-Smad activity and provide a potential avenue for LC-PUFAs to influence a variety of developmental processes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Miyares, Rosa Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Stein, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Renisch, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Anderson, Jennifer Lynn UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Farber, Steven Arthur UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-469910
DOI:	10.1016/j.devcel.2013.11.011
Journal or Publication Title:	Dev. Cell
Volume:	27
Number:	6
Page Range:	S. 635 - 648
Date:	2013
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1878-1551
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLYUNSATURATED FATTY-ACIDS; ACTIVATED PROTEIN-KINASE; GLYCOGEN-SYNTHASE KINASE-3; TGF-BETA RECEPTOR; P38 MAPK; EICOSAPENTAENOIC ACID; SIGNALING PATHWAY; ALPORT-SYNDROME; BMP; GENE Multiple languages Cell Biology; Developmental Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/46991