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PLoS One 2009 Aug 06;48:e6543. doi: 10.1371/journal.pone.0006543.
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Mad is required for wingless signaling in wing development and segment patterning in Drosophila.

Eivers E , Fuentealba LC , Sander V , Clemens JC , Hartnett L , De Robertis EM .

A key question in developmental biology is how growth factor signals are integrated to generate pattern. In this study we investigated the integration of the Drosophila BMP and Wingless/GSK3 signaling pathways via phosphorylations of the transcription factor Mad. Wingless was found to regulate the phosphorylation of Mad by GSK3 in vivo. In epistatic experiments, the effects of Wingless on wing disc molecular markers (senseless, distalless and vestigial) were suppressed by depletion of Mad with RNAi. Wingless overexpression phenotypes, such as formation of ectopic wing margins, were induced by Mad GSK3 phosphorylation-resistant mutant protein. Unexpectedly, we found that Mad phosphorylation by GSK3 and MAPK occurred in segmental patterns. Mad depletion or overexpression produced Wingless-like embryonic segmentation phenotypes. In Xenopus embryos, segmental border formation was disrupted by Smad8 depletion. The results show that Mad is required for Wingless signaling and for the integration of gradients of positional information.

PubMed ID: 19657393
PMC ID: PMC2717371
Article link: PLoS One
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cnga1 ctnnb1 dspp egfr egr2 gsk3b lgals4.2 mad1l1 mapk1 mlc1 myod1 nkd1 otx2 ptch1 rax smad1 smad7 smad9 sox2 szl tbx2 wnt10b wnt3a
Morpholinos: smad9 MO1

Article Images: [+] show captions
References [+] :
Affolter, Multiple requirements for the receptor serine/threonine kinase thick veins reveal novel functions of TGF beta homologs during Drosophila embryogenesis. 1994, Pubmed