Van Blerkom J, Janzen R, Runner M N
J Embryol Exp Morphol. 1982 Dec;72:97-116.
The extent to which differential gene expressions can be correlated with organ development was examined at the level of protein synthesis during pre- and postnatal development in the mouse. High resolution, equilibrium, two-dimensional polyacrylamide gel electrophoresis detected, for each of five to ten successive stages for each of seven organ systems, between 850 and 1000 separate newly synthesized proteins. The possibility that the 1000 detectable proteins synthesized at any one time during organ development represent a sampling bias was contra-indicated (a) because a different and larger population of [14C]amino acid-incorporating protein syntheses gave similar results and (b) because nonequilibrium isoelectric focusing, electrophoresis, isoelectric points between pH 5.5 and 8.7 confirmed the results from yet a different population of protein syntheses. Within limits of the sampling of protein syntheses, the entire period of organ development examined proceeds with altered expression of small proportion of the total proteins being synthesized. While all protein changes were stage specific, approximately three organ-specific protein syntheses were detected per organ system. One family of five protein syntheses seen in 16-day foetuses had homologous primary structures and presumably are keratins derived from a single genomic expression. These selected stage-specific protein syntheses examined by electrophoresis of partial proteolytic digests disclosed a programme for post-translational changes in protein syntheses. The current observations indicate that the examined pre- and postnatal organ development of the seven organs occurs in the presence of greater than 99% similarity among proteins synthesized in the same and different organ systems. Functional differentiation during organogenesis, therefore, occurs in the presence of less than 1% change in qualitative or quantitative switch in protein syntheses. Evidence is presented to indicate that even this remarkably small number of changes in protein syntheses during functional organ differentiation may be derived from an even smaller subset of gene expressions. Collectively, the data suggest that explanatory mechanisms for molecular organogenesis must encompass both selective gene expressions along with post-translational programmed events.
在小鼠出生前和出生后的发育过程中，从蛋白质合成水平研究了差异基因表达与器官发育的关联程度。高分辨率、平衡的二维聚丙烯酰胺凝胶电泳在七个器官系统中，每个系统的五到十个连续发育阶段，检测到850至1000种单独的新合成蛋白质。在器官发育的任何一个时间点合成的1000种可检测蛋白质存在抽样偏差的可能性被排除，原因如下：（a）因为不同且更大数量的掺入[14C]氨基酸的蛋白质合成给出了相似结果；（b）因为非平衡等电聚焦电泳（pH 5.5至8.7之间的等电点）证实了来自另一不同蛋白质合成群体的结果。在蛋白质合成抽样的范围内，所研究的器官发育全过程中，只有一小部分正在合成的蛋白质的表达发生了变化。虽然所有蛋白质变化都是阶段特异性的，但每个器官系统大约检测到三种器官特异性蛋白质合成。在16天胎儿中观察到的一组五种蛋白质合成具有同源一级结构，推测是源自单一基因组表达的角蛋白。通过部分蛋白酶解消化产物的电泳研究这些选定的阶段特异性蛋白质合成，揭示了蛋白质合成后翻译变化的程序。目前的观察结果表明，所研究的七个器官在出生前和出生后的发育过程中，同一器官系统和不同器官系统合成的蛋白质之间相似度超过99%。因此，器官发生过程中的功能分化是在蛋白质合成的定性或定量转换变化小于1%的情况下发生的。有证据表明，即使在功能器官分化过程中蛋白质合成的变化数量非常少，也可能源自更小的基因表达子集。总体而言，这些数据表明，分子器官发生的解释机制必须既包括选择性基因表达，也包括翻译后程序性事件。
