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???displayArticle.abstract??? Snail family transcriptional repressors regulate epithelial mesenchymal transitions during physiological and pathological processes. A conserved SNAG repression domain present in all vertebrate Snail proteins is necessary for repressor complex assembly. Here, we identify the Ajuba family of LIM proteins as functional corepressors of the Snail family via an interaction with the SNAG domain. Ajuba LIM proteins interact with Snail in the nucleus on endogenous E-cadherin promoters and contribute to Snail-dependent repression of E-cadherin. Using Xenopus neural crest as a model of in vivo Snail- or Slug-induced EMT, we demonstrate that Ajuba LIM proteins contribute to neural crest development as Snail/Slug corepressors and are required for in vivo Snail/Slug function. Because Ajuba LIM proteins are also components of adherens junctions and contribute to their assembly or stability, their functional interaction with Snail proteins in the nucleus suggests that Ajuba LIM proteins are important regulators of epithelia dynamics communicating surface events with nuclear responses.
Figure 4. Ajuba LIM Protein Expression in Xenopus Embryos Enhances Neural Crest Development in a Slug-Dependent Manner(A) X. laevis embryos coinjected with β-gal and either XSlug, XSnail, mAjuba, mLIMD1, mWTIP, XLIMD1, or XWTIP capped mRNAs were fixed at stage 18 and in situ hybridization performed for XSlug.(B) Graph displaying the percent of embryos with increased neural crest on the injected side (by Slug in situ hybridization). The total number of embryos injected is shown over each column (n).(C) X. laevis embryos were coinjected with β-gal and the XSlug MO alone or in combination with XLIMD1, XWTIP, or XSlug mRNA, and in situ hybridization for Twist performed.(D) Graph displaying the percent of embryos with decreased neural crest on the injected side (by Twist in situ hybridization). The total number of embryos injected is shown over each column (n).
Figure 5. Depletion of XLIMD1 or XWTIP Blocks Neural Crest Development in Xenopus(A) X. laevis embryos were coinjected with β-gal and control MO, XLIMD1 MO (20 ng), XWTIP MO (10 ng), or a combination of XLIMD1 and XWTIP MOs. Embryos were fixed at stage 18–19, and in situ hybridization for XSlug or XTwist performed.(B) Graph displaying percent of embryos with decreased neural crest on injected side by Slug or Twist in situ hybridization following injection of low dose (gray columns; 10 ng XLIMD1 MO, 5 ng XWTIP MO) or high dose (black columns; 20 ng XLIMD1 MO, 10 ng XWTIP MO) of morpholinos. The total number of embryos injected is shown over each column (n).(C) X. laevis embryos were coinjected with β-gal, the XWTIP MO (5 ng) and XWTIP capped mRNA as shown. Black columns indicate the percent of embryos with decreased neural crest on the injected side (by Slug or Twist in situ) and white columns indicate the percent of embryos where neural crest was the same on the injected and uninjected sides. The total number of embryos injected is shown over each set of columns (n).
Figure 7. Ajuba LIM Proteins Affect Cell Survival and Border Territories without Affecting Proliferation(A) X. laevis embryos were injected with XSlug or XLIMD1 mRNA, fixed at stage 16, and immunohistochemistry performed for phosphohistone-H3.(B) X. laevis embryos were injected with XSlug MO or a combination of XLIMD1 +XWTIP MOs. Embryos were fixed at stage 16 and TUNEL staining performed. The number of embryos displaying increased TUNEL staining on the injected side over the total number of embryos analyzed is shown in the bottom right corner.(C) X. laevis embryos were injected with MOs as shown, fixed at stage 16, and in situ hybridization performed for Epiker (epidermal) and Sox2 (neural).
Figure 8. Depletion of Both XLIMD1 and XWTIP Blocks Slug Repressor Activity during Neural Crest Development in Xenopus(A) X. laevis embryos were coinjected with β-gal, XLIMD1 MO (5 ng) and XWTIP MO (10ng) alone or in combination with XSlug, SlZnF, or EngR.SlZnF capped mRNA. Embryos were fixed at stage 18–19 and in situ hybridization performed for XSlug.(B) Graph displaying the percent of embryos with decreased neural crest on the injected side by Slug in situs (following injection of MOs and RNAs as shown). The total number of embryos injected is shown over each column (n).
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