Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching Journal Article

  

Authors:	Rakeman, A. S.; Anderson, K. V.
Article Title:	Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching
Abstract:	Dynamic cell movements and rearrangements are essential for the generation of the mammalian body plan, although relatively little is known about the genes that coordinate cell movement and cell fate. WAVE complexes are regulators of the actin cytoskeleton that couple extracellular signals to polarized cell movement. Here, we show that mouse embryos that lack Nap1, a regulatory component of the WAVE complex, arrest at midgestation and have defects in morphogenesis of all three embryonic germ layers. WAVE protein is not detectable in Nap1 mutants, and other components of the WAVE complex fail to localize to the surface of Nap1 mutant cells; thus loss of Nap1 appears to inactivate the WAVE complex in vivo. Nap1 mutants show specific morphogenetic defects: they fail to close the neural tube, fail to form a single heart tube (cardia bifida), and show delayed migration of endoderm and mesoderm. Other morphogenetic processes appear to proceed normally in the absence of Nap1/WAVE activity: the notochord, the layers of the heart, and the epithelial-to-mesenchymal transition (EMT) at gastrulation appear normal. A striking phenotype seen in approximately one quarter of Nap1 mutants is the duplication of the anteroposterior body axis. The axis duplications arise because Nap1 is required for the normal polarization and migration of cells of the Anterior Visceral Endoderm (AVE), an early extraembryonic organizer tissue. Thus, the Nap1 mutant phenotypes define the crucial roles of Nap1/WAVE-mediated actin regulation in tissue organization and establishment of the body plan of the mammalian embryo.
Keywords:	controlled study; unclassified drug; nonhuman; pathophysiology; protein function; protein localization; animal cell; mouse; phenotype; mammalia; animals; mice; actin; animal tissue; embryo; protein depletion; protein protein interaction; membrane proteins; embryo development; embryo pattern formation; gene function; morphogenesis; regulatory mechanism; amino acid sequence; molecular sequence data; cell membrane; cell migration; cell movement; gene duplication; cell polarity; mouse strain; actins; mesoderm; genetic code; protein determination; polarization; congenital heart malformation; embryonic development; endoderm; viscera; heart development; chromosome mapping; regulator protein; mouse embryo; embryonal tissue; genes, lethal; gastrulation; neural tube defect; cell surface; anterior posterior axis; germ layer; notochord; axis specification; gestation period; pseudopodia; wiskott-aldrich syndrome protein family; nap1; wave; protein nap1; protein wave
Journal Title:	Development
Volume:	133
Issue:	16
ISSN:	0950-1991
Publisher:	Company of Biologists
Date Published:	2006-08-15
Start Page:	3075
End Page:	3083
Language:	English
DOI:	10.1242/dev.02473
PUBMED:	16831833
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33748796067&partnerID=40&md5=5e954a20198903a136abc191b82ac873
Notes:	--- - "Cited By (since 1996): 33" - "Export Date: 4 June 2012" - "CODEN: DEVPE" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/27916