000217822 001__ 217822
000217822 005__ 20181203024224.0
000217822 0247_ $$2doi$$a10.1242/dev.127506
000217822 022__ $$a0950-1991
000217822 02470 $$2ISI$$a000369500200010
000217822 037__ $$aARTICLE
000217822 245__ $$aRING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression
000217822 260__ $$aCambridge$$bCompany Of Biologists Ltd$$c2016
000217822 269__ $$a2016
000217822 300__ $$a10
000217822 336__ $$aJournal Articles
000217822 520__ $$aPolycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in Ring1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the Ring1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry.
000217822 6531_ $$aMeis
000217822 6531_ $$aMouse limb development
000217822 6531_ $$aPolycomb
000217822 6531_ $$aProximal-distal specification
000217822 6531_ $$aRING1
000217822 700__ $$aYakushiji-Kaminatsui, Nayuta$$uRIKEN, Ctr Integrat Med Sci IMS, Lab Dev Genet, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
000217822 700__ $$aKondo, Takashi$$uRIKEN, Ctr Integrat Med Sci IMS, Lab Dev Genet, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
000217822 700__ $$aEndo, Takaho A.$$uRIKEN IMS, Lab Integrat Genom, Tsurumi Ku, 1-7-22 Suehirocho, Yokohama, Kanagawa 2300045, Japan
000217822 700__ $$aKoseki, Yoko$$uRIKEN, Ctr Integrat Med Sci IMS, Lab Dev Genet, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
000217822 700__ $$aKondo, Kaori$$uRIKEN, Ctr Integrat Med Sci IMS, Lab Dev Genet, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
000217822 700__ $$aOhara, Osamu$$uRIKEN IMS, Lab Integrat Genom, Tsurumi Ku, 1-7-22 Suehirocho, Yokohama, Kanagawa 2300045, Japan
000217822 700__ $$aVidal, Miguel$$uCtr Invest Biol, Dept Cellular & Mol Biol, Ramiro de Maeztu 9, Madrid 28040, Spain
000217822 700__ $$aKoseki, Haruhiko$$uRIKEN, Ctr Integrat Med Sci IMS, Lab Dev Genet, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan
000217822 773__ $$j143$$k2$$q276-285$$tDevelopment
000217822 909C0 $$0252450$$pISREC$$xU11153
000217822 909CO $$ooai:infoscience.tind.io:217822$$pSV$$particle
000217822 917Z8 $$x148230
000217822 937__ $$aEPFL-ARTICLE-217822
000217822 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000217822 980__ $$aARTICLE