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

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.

Novel Insights into Chromosome Evolution in Birds, Archosaurs, and Reptiles

“…A bird-specific CNE found 100 bp upstream from BMPR1B contains two transcription factor binding sites (TFBSs) for AP-1 (known as cJun ) and NF-E4 . The AP-1 transcription factor superfamily plays a role in the regulation of apoptosis during limb development in chickens (Suda et al 2014), and could account for the reported differences in expression of BMPR1B in birds compared to other vertebrates (Brawand et al 2011). Therefore, the presence of this CNE containing a relevant TFBS could have contributed to the formation and stability of this msHSB in avian evolution.…”

Genetic variants of 20q12 contributed to non‐syndromic orofacial clefts susceptibility

“…MAFB was a favorable candidate gene of NSOC. It belongs to the MAF family of transcription factors characterized by a typical bZip structure and acts as an important regulator during the development and differentiation of many organs and tissues including orofacial development (Dixon et al , ; Suda et al , ; Tsuchiya et al , ). It was expressed in both craniofacial ectoderm and neural crest‐derived mesoderm between E13.5 and E14.5 in mouse models.…”

Reduction in cadmium‐induced toxicity by c‐Jun modulation in mouse embryo limb bud cells

“…This is not unexpected since c‐Jun has been linked to a variety of developmental processes. Most importantly, dimers of the AP‐1 transcription factor members, c‐Jun and MafB, play a role in the induction of apoptosis in developing chick limbs (Suda et al, ). c‐Jun has also been found to be a key component of the signaling pathway that leads to joint formation in developing limbs (Kan and Tabin, ).…”