Eric H. Davidson

Genetic information in oocyte RNA.

RNA of the mature Xenopus oocyte was hybridized with the isolated non-repetitive DNA fraction of the Xenopus genome. The hybrids had the thermal stability and other characteristics expected of non-repetitive DNA-RNA hybrids, and DNA recovered from them reassociated at the rate of non-repetitive DNA. By saturating the non-repetitive DNA with Oocyte RNA a direct minimum estimate was obtained of the amount of non-repetitive sequence in the oocyte RNA, i.e. its genomic information content. The oocyte RNA contains about 20 × 10^6 nucleotide pairs of diverse sequence, which is 4.5 times the total genomic information present in the Escherichia coli chromosome.

Note on the control of gene expression during development

The process of development is interpreted in terms of a recent theory of gene regulation. In that theory agents interact with sensor structures associated with the genome. It was proposed that these interactions lead to the transcription of integrator genes and their products in turn effect control of the transcription of many genes and establish patterns of gene activation. The elements of the theory appear sufficient, in principle, to explain the process of development. We assume that there exists an initial divergence in genetic activity due to an unequal distribution of egg cytoplasmic regulatory elements among the different cells in early cleavage. As a result particular sensor structures could be synthesized in some cells and not in others. Therefore, individual cells would differ in their response to external inductive agents arising, for example, in nearby cell layers. Each specific cell or cell type would then be characterized by the integrated activation of a proper set of genes and be capable of carrying out its role in subsequent developmental events.

The variable gene activity theory of cell differentiation

This chapter presents the variable gene activity theory of cell differentiation. Several premises are required in arriving at the proposition that differentiation is a function of variable gene activity. First among these is the now well-understood molecular relationship between the genetic DNA and the structure of the various proteins found in the cell. The second premise of the argument for the variable gene activity theory is the proposition that every living cell nucleus in a metazoan organism contains the same complete xa0[A1]

The onset of genome control in embryogenesis

This chapter describes the onset of genome control in embryogenesis. The earliest stages of embryonic life also involve a certain amount of actual morphogenesis, in particular the construction of characteristic pregastrular structures, such as the hollow blastula of the echinoderm, or the structures demarcating the germinal layers from the nutrient syncytium in meroblastic eggs. Though specialized cellular structures, thus, exist even at these very early periods, pregastrular cells appear in general to be functionally nondifferentiated, at least in comparison to the situation following gastrulation when a variety of clearly specialized functional tissues has come into being. Differentiation in this discussion is defined as xa0[A2]

Gene activity in the oocyte nucleus: synthesis of informational RNA

Though most of the RNA synthesized during oogenesis and stored in the mature oocyte is ribosomal, it is obvious that ribosomal RNA itself cannot account for the known properties of the RNA stockpile carried in the egg cytoplasm. Amphibian embryos, according to Brown and Littna, contain sizable quantities of informational RNA that is synthesized during the very last hours of oogenesis. Lampbrush chromosome structure has long been considered suggestive of intense and widespread gene activity. Lampbrush chromosome structure has long been considered suggestive of intense and widespread gene activity. The chromosomes attain their maximum degree of extension at the mid-lampbrush stage (stage 4), and the linear, alternating, loop-chromomere arrangement suggests the linear arrangement of genetic sites in the genome. It is known that each loop contains one D N A duplex, and each pair of loops and each chromosome two such duplexes.

Interpretations of the localization phenomenon

This chapter reviews the interpretations of the localization phenomenon. Since localization affects the course of differentiation, it would seem clear that it must be explained in terms of the regulation of embryo genome function. It was generally believed in Wilsons time that all cells contain the complete genome and also that genes direct the cellular construction of properties. Nevertheless, it was not until much later that the theory of variable gene activity was clearly enunciated as an explanation for cell differentiation. The failure to take this conceptual step prevented the earlier writers from proceeding beyond the idea of organ-forming substances. Storage in the egg cytoplasm of molecules whose function is the selective specification of embryo gene activity is an extremely general and probably universal mechanism in animal development.

1 – Origin and differentiation of the female germ line

This chapter provides an overview of the origin and differentiation of the female germ line. The germ cells are often easy to recognize, standing out from the adjacent cells by virtue of their larger size and prominent nuclei. Even where the primordial germ-line stem cells have not been traced back to the very beginning of embryogenesis, they are reported in most cases to be established at least as early as gastrulation. The chapter presents the general aspects of the timing of oogenesis in the chordate life cycle, oogenesis in sea urchins, panoistic and meroistic insect oogenesis, the occurrence of lampbrush chromosomes and the duration of the lampbrush stage, and the synopsis of the temporal aspects of female germ-line differentiation.

The localization phenomenon

This chapter provides an overview of the localization phenomenon. Localization is the phenomenon of precocious specification of future cell fate and precocious limitation of morphogenetic potential very early in embryogenesis, long before the cells in question manifest their morphogenetic fates. In cases of localization, the differentiation of a given line of cells can be regarded as a function of the particular areas of cytoplasm inherited early in embryogenesis by the stem cells of that cell lineage. Localized areas of future cell fate can often be mapped out on the uncleaved egg cytoplasm and can be tested for at the earliest cleavage stages; where localization precedes fertilizatio; this is sometimes referred to as prelocalization. xa0[A5]

Early molecular indices of differentiation

This chapter provides an overview of the early molecular indices of differentiation. Differentiation, by definition, is associated with change in the population of protein molecules in the differentiating cells. The chapter discusses several studies of a direct assay of change in the patterns of protein synthesis in actinomycin-treated sea urchin embryos. Though it is clear that a novel set of proteins is assembled by gastrulation, what functions these proteins actually perform or what enzymic activities they include is for the most part not known. A number of particular enzymic activities have been observed to increase sharply, beginning at gastrulation. However, in most such studies, it is difficult to be certain that what is measured is the de novo synthesis of new protein molecule rather than activation or recombination of enzyme subunits that had perhaps been stored in the egg cytoplasm from the time of oogenesis. There are certain cases, however, in which it is demonstrable that new histospecific proteins do indeed make their appearance as the tissues requiring their function differentiate.

Characteristics of bacterial repression-derepression systems

This chapter provides an overview of the characteristics of bacterial repression–derepression systems. It discusses an unsolved problem of the actual nature of the genomic regulation machinery operating in differentiated cells. Frequent attempts have been made to apply to this problem the bacterial repression–derepression models of gene regulation originally suggested by Jacob and Monod. The chapter describes polycistronic messenger RNA, the operator gene concept, and regulatory genes in coordinate and other systems. Where coordinate control exists, it is based on the synthesis of polycistronic messenger RNA. Polycistronic template R N A products of the lac operon in E. coli have been demonstrated by Kiho and Rich, who utilized various deletion mutants lacking certain regions of the operon. Sedimentation analyses of the polysomal populations in induced cells show that s-galactosidase is synthesized on polysomes and that these polysomes are of larger size in wild-type E. coli than in mutants synthesizing galactosidase but bearing deletions in the transacetylase region.