GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis.
GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis.
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DOI：
10.1016/j.devcel.2012.01.006
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发表时间：
2012-04-17
影响因子：
11.8
通讯作者：
Zeller, Rolf
中科院分区：
文献类型：
--
作者：
Lopez-Rios, Javier;Speziale, Dario;Robay, Dimitri;Scotti, Martina;Osterwalder, Marco;Nusspaumer, Gretel;Galli, Antonella;Hollaender, Georg A.;Kmita, Marie;Zeller, Rolf
Gli3是脊椎动物中Hedgehog信号的关键组成部分，其失活会导致肢体芽发育过程中形成额外的指（多指）。对先天缺乏Gli3的小鼠胚胎的分析揭示了Gli3在确定前肢轴和手指身份方面的基本功能。在小鼠手板发育过程中，我们有条件地灭活了Gli3，从而使所产生的轴前多指畸形与已知的Gli3在建立AP和数字身份方面的功能分离。我们的分析表明，GLI3直接限制G1-S细胞周期转变的调节因子如Cdk6的表达，并限制手指前板中手指祖细胞的S期进入。此外，GLI3通过时空限制和终止BMP拮抗剂Gremlin1的表达，促进增殖祖细胞向BMP依赖的软骨分化。因此，Gli3是指祖细胞增殖扩张的负调节因子，并作为软骨分化出口的看门人。
Inactivation of Gli3, a key component of Hedgehog signaling in vertebrates, results in formation of additional digits (polydactyly) during limb bud development. The analysis of mouse embryos constitutively lacking Gli3 has revealed the essential GLI3 functions in specifying the anteroposterior (AP) limb axis and digit identities. We conditionally inactivated Gli3 during mouse hand plate development, which uncoupled the resulting preaxial polydactyly from known GLI3 functions in establishing AP and digit identities. Our analysis revealed that GLI3 directly restricts the expression of regulators of the G1–S cell-cycle transition such as Cdk6 and constrains S phase entry of digit progenitors in the anterior hand plate. Furthermore, GLI3 promotes the exit of proliferating progenitors toward BMP-dependent chondrogenic differentiation by spatiotemporally restricting and terminating the expression of the BMP antagonist Gremlin1. Thus, Gli3 is a negative regulator of the proliferative expansion of digit progenitors and acts as a gatekeeper for the exit to chondrogenic differentiation.
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影响因子：
2.6
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McGlinn, E;van Bueren, KL;Wicking, C
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