Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis
Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis
复制标题
DOI：
10.1242/dev.099150
复制
发表时间：
2014-07
期刊：
影响因子：
4.6
通讯作者：
Natsuno Suda;T. Itoh;Ryuichiro Nakato;D. Shirakawa;M. Bando;Y. Katou;K. Kataoka;K. Shirahige;C. Tickle;Mikiko Tanaka
中科院分区：
文献类型：
--
作者：
Natsuno Suda;T. Itoh;Ryuichiro Nakato;D. Shirakawa;M. Bando;Y. Katou;K. Kataoka;K. Shirahige;C. Tickle;Mikiko Tanaka
细胞凋亡是细胞形态形成的重要机制。然而，控制肢体芽发育过程中细胞凋亡的分子级联反应在很大程度上仍不清楚。在这里，我们发现MafB在鸡肢体芽的凋亡区域特异性表达，MafB/cFos异二聚体抑制细胞凋亡，而MafB/cJun异二聚体促进细胞凋亡，从而塑造肢体的形状。鸡肢体芽染色质免疫沉淀测序发现了Maf和jun控制的潜在靶基因和调控元件。功能分析显示，mab和cJun直接激活了p63和p73的表达，而p63和p73是阻止细胞周期的关键成分。我们的数据表明，在发育中的鸡肢体芽中，MafB、cFos和cJun的二聚体组合控制着凋亡细胞的数量，并且MafB/cJun异二聚体通过激活p63和p73导致凋亡。
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.