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Development 2011 May 01;13810:2035-47. doi: 10.1242/dev.058800.
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MIM regulates vertebrate neural tube closure.

Liu W , Komiya Y , Mezzacappa C , Khadka DK , Runnels L , Habas R .

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.

PubMed ID: 21471152
PMC ID: PMC3082306
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actl6a daam1 dvl1 dvl2 fmn1 gli1 gsc mtss1 mtss1.2 myc odc1 pax3 ptch1 rho shh smo sox2 tbxt wnt3a wnt8a zic3
Morpholinos: mtss1.2 MO1 mtss1.2 MO2

Phenotypes: Xla Wt + daam1 MO (Fig 6 G) [+]

Article Images: [+] show captions
References [+] :
Asaoka, Identification of a suppressive mechanism for Hedgehog signaling through a novel interaction of Gli with 14-3-3. 2010, Pubmed