Developmental genetics of hepatic gluconeogenic enzymes.
Developmental genetics of hepatic gluconeogenic enzymes.
复制标题
肝糖异生酶的发育遗传学。
DOI：
10.1111/j.1749-6632.1986.tb15524.x
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发表时间：
1986
影响因子：
5.2
通讯作者：
Gluecksohn-Waelsch,S
中科院分区：
文献类型：
--
作者：
Gluecksohn-Waelsch,S
细胞特异性分化是现代分子生物学、遗传学和发育生物学的核心问题之一。高等真核生物体的每个细胞的遗传禀赋的身份，与其细胞和组织类型的异质性相反，提出了关于负责某些基因的细胞特异性表达的机制的问题，与其他基因的抑制相反。分析这些问题的进展在很大程度上取决于选择最适合实验方法的模型系统。在随后的研究中，人们将很难找到一个上级肝脏的系统来分析细胞特异性分化的发育调节。这个器官显然包括各种不同功能的细胞类型。但是，正是一种特殊的细胞，即肝细胞，通过表达一组几乎没有任何其他器官所共有的特定功能，赋予肝脏其特有的区别。在肝脏特异性但异质性的基因产物组中，一组酶脱颖而出，与糖代谢的各个步骤有关，特别是与糖异生有关。相关肝酶的代谢调节及其诱导机制，例如激素，一直是许多实验方法的主题，其中一些包括在本卷的讨论中。然而，我想在这里讨论的问题并不涉及由出生后生物体分化的肝细胞表达的促肝细胞生成酶的代谢调节，而是它们的发育调节。特别是，我建议把重点放在调控机制，在产前分化过程中的形式和功能的肝细胞，这是负责出现一种细胞类型，其中特定的基因被激活和其他repressed.The特定的系统在高等真核生物，已借给自己美丽的探索这些问题是辐射诱导突变的小鼠。在发育遗传学的历史上，突变在为分析发育过程中的基因作用提供实验材料方面发挥了最重要的作用，并且，用最近的一篇评论的话来说，“突变研究提供了基因产物与发育的特定方面之间最强的因果关系。这适用于果蝇和小鼠等彼此不同的生物体，它们都以广泛的遗传学知识为特征，从而促进了它们的发育分析。我所提到的小鼠突变是由罗素夫妇在奥克进行的辐射诱变研究中产生的
One of the central problems in modem molecular biology and genetics as well as developmental biology, is that of the differentiation of cell specificity. The identity of the genetic endowment of each cell of the high eukaryote organism, in contrast to the heterogeneity of its cell and tissue types, raises questions concerning the mechanisms responsible for the cell-specific expression of certain genes in contrast to the repression of others. Progress in the analysis of such problems depends to a considerable degree on the selection of model systems best suited for an experimental approach. In the ensuing search, one would be hard pressed to find a system superior to that of the liver for an analysis of developmental regulation of cell-specific differentiation. This organ obviously includes a variety of cell types with quite different functions. But it is one particular cell, that is, the hepatocyte, that confers on the liver its characteristic distinction by expressing a cluster of specific functions shared by hardly any other organ. Within the group of liver-specific but heterogeneous gene products, a cluster of enzymes stands out that is concerned with various steps in sugar metabolism, in particular with gluconeogenesis. The metabolic regulation of the relevant liver enzymes and the mechanisms of their induction, for example, by hormones, have been the subject of many experimental approaches, some of which are included in the discussions in this volume. The questions that I would like to address here, however, do not concern the metabolic regulation of gluconeogenic enzymes expressed by the differentiated hepatocyte of the postnatal organism, but rather their developmental regulation. In particular, I propose to focus on the mechanisms of regulation that operate in the course of prenatal differentiation of both form and function of hepatocytes and that are responsible for the emergence of a cell type in which specific genes are activated and others repressed.The particular system in high eukaryotes that has lent itself beautifully to an exploration of these questions is that of radiation-induced mutations in the mouse. In the history of developmental genetics, mutations have played a most significant role in offering experimental material for the analysis of gene action during development, and, in the words of a recent review,’“mutational studies provide the strongest causal link between a gene’s product and a particular aspect of development.” This holds true for organisms as different from each other as Drosophila and mice, both of them characterized by extensive knowledge of their genetics, thus facilitating their developmental analysis. The mutations in mice to which I refer were produced in studies of radiation-induced mutagenesis conducted in this country by the Russells at Oak