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Development. 2014 Jul;141(14):2885-94. doi: 10.1242/dev.099150.

Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis.

Author information

1
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-17, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
2
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-34, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
3
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
4
Graduate School of Medical Life Sciences, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
5
Department of Biology and Biochemistry, University of Bath, Claverton Down Road, Bath BA2 7AY, UK.
6
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-17, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan mitanaka@bio.titech.ac.jp.

Abstract

Apoptosis is an important mechanism for sculpting morphology. However, the molecular cascades that control apoptosis in developing limb buds remain largely unclear. Here, we show that MafB was specifically expressed in apoptotic regions of chick limb buds, and MafB/cFos heterodimers repressed apoptosis, whereas MafB/cJun heterodimers promoted apoptosis for sculpting the shape of the limbs. Chromatin immunoprecipitation sequencing in chick limb buds identified potential target genes and regulatory elements controlled by Maf and Jun. Functional analyses revealed that expression of p63 and p73, key components known to arrest the cell cycle, was directly activated by MafB and cJun. Our data suggest that dimeric combinations of MafB, cFos and cJun in developing chick limb buds control the number of apoptotic cells, and that MafB/cJun heterodimers lead to apoptosis via activation of p63 and p73.

KEYWORDS:

AP-1 transcription factor; Chick; Limb

PMID:
25005477
DOI:
10.1242/dev.099150
[Indexed for MEDLINE]
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