Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA; email:
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA; email:
Annu Rev Genet. 2023 Nov 27;57:117-134. doi: 10.1146/annurev-genet-022123-104503.
Organismal development requires the reproducible unfolding of an ordered sequence of discrete steps (cell fate determination, migration, tissue folding, etc.) in both time and space. Here, we review the mechanisms that grant temporal specificity to developmental steps, including molecular clocks and timers. Individual timing mechanisms must be coordinated with each other to maintain the overall developmental sequence. However, phenotypic novelties can also arise through the modification of temporal patterns over the course of evolution. Two main types of variation in temporal patterning characterize interspecies differences in developmental time: allochrony, where the overall developmental sequence is either accelerated or slowed down while maintaining the relative duration of individual steps, and heterochrony, where the duration of specific developmental steps is altered relative to the rest. New advances in in vitro modeling of mammalian development using stem cells have recently enabled the revival of mechanistic studies of allochrony and heterochrony. In both cases, differences in the rate of basic cellular functions such as splicing, translation, protein degradation, and metabolism seem to underlie differences in developmental time. In the coming years, these studies should identify the genetic differences that drive divergence in developmental time between species.
生物体的发育需要在时间和空间上可重复地展开有序的离散步骤(细胞命运决定、迁移、组织折叠等)。在这里,我们回顾了赋予发育步骤时间特异性的机制,包括分子钟和定时器。单个定时机制必须相互协调,以维持整体发育序列。然而,表型的新颖性也可以通过在进化过程中改变时间模式而产生。时间模式变化的两种主要类型表征了发育时间的种间差异:变时性,其中整体发育序列要么加速,要么减速,同时保持单个步骤的相对持续时间,以及异体时性,其中特定发育步骤的持续时间相对于其他步骤发生改变。最近,使用干细胞对哺乳动物发育进行体外建模的新进展使得对变时性和异体时性的机制研究得以复兴。在这两种情况下,基本细胞功能(如剪接、翻译、蛋白质降解和代谢)的速度差异似乎是发育时间差异的基础。在未来几年,这些研究应该确定驱动物种间发育时间差异的遗传差异。
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