Species-specific pace of development is associated with differences in protein stability

被引：153

作者：

Rayon, Teresa ^{[1
]}

Stamataki, Despina ^{[1
]}

Perez-Carrasco, Ruben ^{[1
,2
,3
]}

Garcia-Perez, Lorena ^{[1
]}

Barrington, Christopher ^{[1
]}

Melchionda, Manuela ^{[1
]}

Exelby, Katherine ^{[1
]}

Lazaro, Jorge ^{[1
]}

Tybulewicz, Victor L. J. ^{[1
,4
]}

Fisher, Elizabeth M. C. ^{[5
]}

Briscoe, James ^{[1
]}

机构：

[1] Francis Crick Inst, London NW1 1AT, England

[2] UCL, Dept Math, London WC1E 6BT, England

[3] Imperial Coll London, Dept Life Sci, London SW7 2AZ, England

[4] Imperial Coll, Dept Immunol & Inflammat, London W12 0NN, England

[5] UCL, UCL Queen Sq Inst Neurol, London WC1N 3BG, England

来源：

SCIENCE | 2020年 / 369卷 / 6510期

基金：

欧洲研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

SONIC HEDGEHOG; CELL-CYCLE; QUALITY-CONTROL; NEURAL-TUBE; RADIAL GLIA; GRADIENT; DIFFERENTIATION; FRAMEWORK; DYNAMICS; MODELS;

D O I：

10.1126/science.aba7667

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which the embryo develops can vary substantially between species. For example, the same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the program runs more than twice as fast in mouse as in human. This is not due to differences in signaling, nor the genomic sequence of genes or their regulatory elements. Instead, there is an approximately two-fold increase in protein stability and cell cycle duration in human cells compared with mouse cells. This can account for the slower pace of human development and suggests that differences in protein turnover play a role in interspecies differences in developmental tempo.

引用

页码：1449 / +

页数：42

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