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Development August 1, 2006; 133 (15): 2845-54.
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Metastasis-associated kinase modulates Wnt signaling to regulate brain patterning and morphogenesis.

Kibardin A , Ossipova O , Sokol SY .

Wnt signaling is a major pathway regulating cell fate determination, cell proliferation and cell movements in vertebrate embryos. Distinct branches of this pathway activate beta-catenin/TCF target genes and modulate morphogenetic movements in embryonic tissues by reorganizing the cytoskeleton. The selection of different molecular targets in the pathway is driven by multiple phosphorylation events. Here, we report that metastasis-associated kinase (MAK) is a novel regulator of Wnt signaling during morphogenetic movements, and eye and brain development in Xenopus embryos. Injected MAK RNA suppressed Wnt transcriptional reporters and activated Jun N-terminal kinase. Furthermore, MAK was recruited to the cell membrane by Frizzled 3, formed a complex with Dishevelled and phosphorylated Dsh in vitro. The regional brain markers Otx2, En2 and Gbx2 were affected in embryos with modulated MAK activity in a manner consistent with a role for MAK in midbrain-hindbrain boundary formation. Confirming the inhibitory role for this kinase in Wnt/beta-catenin signaling, the midbrain patterning defects in embryos depleted of MAK were rescued by the simultaneous depletion of beta-catenin. These findings indicate that MAK may function in different developmental processes as a switch between the canonical and non-canonical branches of Wnt signaling.

PubMed ID: 16790480
PMC ID: PMC4428341
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: chrd.1 dvl1 dvl2 egr2 en2 fzd2 fzd3 fzd8 gal.2 gbx2.1 gbx2.2 gsc hunk jun mak mapk8 myc myod1 nuak1 otx2
Morpholinos: ctnnb1 MO1 hunk MO1

Article Images: [+] show captions
References [+] :
Axelrod, Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. 1998, Pubmed, Xenbase