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First published online May 16, 2007
doi: 10.1242/10.1242/dev.000885

Development 134, 2007-2016 (2007)
Published by The Company of Biologists 2007
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The FERM protein Epb4.1l5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo

Jeffrey D. Lee1, Nancy F. Silva-Gagliardi2, Ulrich Tepass3, C. Jane McGlade2 and Kathryn V. Anderson1,*

1 Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
2 The Hospital for Sick Children, Arthur and Sonia Labatt Brain Tumor Research Center and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
3 Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.

* Author for correspondence (e-mail: k-anderson{at}ski.mskcc.org)

Accepted 20 March 2007

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.

Key words: FERM, Epithelial morphogenesis, EMT, Cytoskeleton, Gastrulation, Actin, Crumbs, Mouse




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[Abstract] [Full Text] [PDF]


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