title: MIM regulates vertebrate neural tube closure.
abstract: Neural tube closure is a critical morphogenetic event that is regulated by dynamic changes in cell shape and behavior. Although previous studies have uncovered a central role for the non-canonical Wnt signaling pathway in neural tube closure, the underlying mechanism remains poorly resolved. Here, we show that the missing in metastasis (MIM; Mtss1) protein, previously identified as a Hedgehog response gene and actin and membrane remodeling protein, specifically binds to Daam1 and couples non-canonical Wnt signaling to neural tube closure. MIM binds to a conserved domain within Daam1, and this interaction is positively regulated by Wnt stimulation. Spatial expression of MIM is enriched in the anterior neural plate and neural folds, and depletion of MIM specifically inhibits anterior neural fold closure without affecting convergent extension movements or mesoderm cell fate specification. Particularly, we find that MIM is required for neural fold elevation and apical constriction along with cell polarization and elongation in both the superficial and deep layers of the anterior neural plate. The function of MIM during neural tube closure requires both its membrane-remodeling domain and its actin-binding domain. Finally, we show that the effect of MIM on neural tube closure is not due to modulation of Hedgehog signaling in the Xenopus embryo. Together, our studies define a morphogenetic pathway involving Daam1 and MIM that transduces non-canonical Wnt signaling for the cytoskeletal changes and membrane dynamics required for vertebrate neural tube closure.
authors.affiliation: Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Komiya
authors.forename: Courtney
authors.initials: C
authors.lastname: Mezzacappa
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Khadka
authors.forename: Loren
authors.initials: L
authors.lastname: Runnels
authors.forename: Raymond
authors.initials: R
authors.lastname: Habas
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017124:Conserved Sequence; D003599:Cytoskeleton / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C443939:Daam1 protein, Xenopus; D053823:Hedgehog Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins