The FERM protein Epb4.1I5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo Journal Article


Authors: Lee, J. D.; Silva-Gagliardi, N. F.; Tepass, U.; McGlade, C. J.; Anderson, K. V.
Article Title: The FERM protein Epb4.1I5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo
Abstract: During early mouse development, a single-layered epithelium is transformed into the three germ layers that are the basis of the embryonic body plan. Here we describe an ENU-induced mutation, limulus (lulu), which disrupts gastrulation and the organization of all three embryonic germ layers. Positional cloning and analysis of additional alleles show that lulu is a null allele of the FERM-domain gene erythrocyte protein band 4.1-like 5 (Epb4.1l5). During gastrulation, some cells in lulu mutants are trapped in the primitive streak at an intermediate stage of the epithelial-mesenchymal transition; as a result, the embryos have very little paraxial mesoderm. Epithelial layers of the later lulu embryo are also disrupted: definitive endoderm is specified but does not form a gut tube, and the neural plate is broad and forms ectopic folds rather than closing to make the neural tube. In contrast to zebrafish and Drosophila, in which orthologs of Epb4.1l5 control the apical localization and activity of Crumbs proteins, mouse Crumbs proteins are localized normally to the apical surface of the lulu mutant epiblast and neural plate. However, the defects in both the lulu primitive streak and neural plate are associated with disruption of the normal organization of the actin cytoskeleton. We propose that mouse Lulu (Epb4.1l5) helps anchor the actin-myosin contractile machinery to the membrane to allow the dynamic rearrangements of epithelia that mediate embryonic morphogenesis.
Keywords: immunohistochemistry; controlled study; gene mutation; mutation; nonhuman; protein domain; protein function; protein localization; animal cell; mouse; animals; mice; actin; allele; animal tissue; mesenchyme cell; embryo; membrane proteins; embryo development; morphogenesis; cell differentiation; in situ hybridization; molecular cloning; tissue distribution; epithelium cell; species difference; epithelium; indoles; cytoskeleton; mesoderm; mutagenesis; neural tube; endoderm; danio rerio; emt; ezrin; moesin; radixin; gastrulation; galactosides; crumbs; neuroectoderm; neural plate; primitive streak; cell disruption; epithelial morphogenesis; ferm; erythrocyte band 4.1 protein; actin myosin interaction; limulus
Journal Title: Development
Volume: 134
Issue: 11
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2007-06-01
Start Page: 2007
End Page: 2016
Language: English
DOI: 10.1242/dev.000885
PUBMED: 17507402
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 21" - "Export Date: 17 November 2011" - "CODEN: DEVPE" - "Source: Scopus"
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  1. Jeffrey D Lee
    8 Lee
  2. Kathryn Anderson
    148 Anderson