Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching.
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.
Rakeman
Andrew S
AS
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
Anderson
Kathryn V
KV
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement; D002874:Chromosome Mapping; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D005804:Genes, Lethal; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D011554:Pseudopodia / Q000235:genetics; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000032:analysis / Q000378:metabolism*
D000199:Actins; D008565:Membrane Proteins; C502089:Nckap1 protein, mouse; C495774:Wasf1 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family