Proneural basic helix-loop-helix proteins and epidermal growth factor receptor signaling coordinately regulate cell type specification and cdk inhibitor expression during development
Proneural basic helix-loop-helix proteins and epidermal growth factor receptor signaling coordinately regulate cell type specification and cdk inhibitor expression during development
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DOI：
10.1128/mcb.01685-06
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发表时间：
2007-04-01
影响因子：
5.3
通讯作者：
Du, Wei
中科院分区：
文献类型：
--
作者：
Sukhanova, Madina J.;Deb, Dilip K.;Du, Wei
在发育过程中，细胞分化和细胞周期退出受到协调调节;然而，这种调节的分子逻辑尚不清楚。果蝇cdk抑制剂Dacapo（Dap）是一种重要的细胞周期调控因子，在发育过程中动态表达，参与细胞周期的发育调控。在这项研究中，Dap表达的调节过程中的细胞类型的规范进行了调查。发现Dap在发育中的眼睛的R2和R5前体中以及在新招募的腿盘股骨感觉器官前体中的表达受表皮生长因子受体信号调节转录因子Pointed（Pnt）和前神经碱性螺旋-环-螺旋蛋白Atonal（Ato）和Daughterless（Da）控制。我们发现，把，Ato和Da调节Dap表达直接通过其各自的结合位点的时候，这些转录因子的功能，以指定神经的命运。这些结果表明，Dap的表达是直接调节的发育机制，同时控制细胞类型的规范。这可能是一种一般机制，通过这种机制，关键细胞周期调节因子的表达与正常发育过程中的分化相协调。分化因子对关键细胞周期调节因子的直接调节确保了细胞周期和分化的协调调节。
Cell differentiation and cell cycle exit are coordinately regulated during development; however, the molecular logic underlying this regulation is not known. The Drosophila cdk inhibitor Dacapo (Dap) is one of the key cell cycle regulators that exhibit dynamic expression during development and contribute to the developmental regulation of the cell cycle. In this study, regulation of Dap expression during cell type specification was investigated. The expression of Dap in the R2 and R5 precursors of the developing eye and in the newly recruited leg disc femoral sense organ precursors was found to be controlled by the epidermal growth factor receptor signaling-regulated transcription factor Pointed (Pnt) and the proneural basic helix-loop-helix proteins Atonal (Ato) and Daughterless (Da). We show that Put, Ato, and Da regulate Dap expression directly through their respective binding sites precisely at the time when these transcription factors function to specify neural fates. These results show that Dap expression is directly regulated by developmental mechanisms that simultaneously control cell type specification. This is potentially a general mechanism by which the expression of key cell cycle regulators is coordinated with differentiation during normal development. The direct regulation of key cell cycle regulators by the differentiation factors ensures coordinated regulation of cell cycle and differentiation.