胚胎氧水平变化调控肢体起始的异时发育
Shifts in embryonic oxygen levels cue heterochrony in limb initiation
异时发育（发育时序的改变）是进化变化的重要机制：鸟类前后肢同步生长，而哺乳动物的后肢发育滞后。本研究发现，这种差异在肢体芽形成之初就已出现，并伴随 T 盒转录因子的异时表达。有趣的是，这一时序差异并非源于控制 T 盒基因表达的顺式调控序列改变，而是取决于鸟类与哺乳动物胚胎在肢体起始前所处的不同氧水平，部分由核因子 κB（NF-κB）家族的转录因子 cRel 和氧感应转录因子缺氧诱导因子 α（Hif1a）介导。研究为发育异时性提供了机制解释，也说明母体环境可调控胚胎发育时序。
为什么推荐给您：揭示氧水平经 Hif1a/cRel 调控肢体发育时序的新机制，属重要发育生物学发现
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摘要Abstract
Heterochrony, or the alteration of developmental timing, is an important mechanism of evolutionary change. Avian species display synchronized growth of the forelimbs and hindlimbs, while mammalian species show delayed hindlimb development. We find that mammalian limb heterochrony is evident from the start of limb bud formation and is associated with heterochronic expression of T-box transcription factors. This heterochronic shift is not due to changes in cis-regulatory sequences controlling T-box gene expression but, unexpectedly, is dependent upon the differential oxygen levels to which avian and mammalian embryos are exposed prior to limb initiation. This is mediated, at least partially, by cRel, a transcription factor in the nuclear factor κB (NF-κB) family, and by the oxygen-sensing transcription factor hypoxia-inducible factor alpha (Hif1a). Together, these results provide a mechanistic understanding of an important example of developmental heterochrony and exemplify how the maternal environment can regulate timing during embryonic development.