Growth Factors in Mammalian Development

I. Y. Rosenblum

• Publisher: CRC Press
• Year: 2021
• ISBN:
  9781000446296
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

The purpose of this volume is to review and discuss key growth factor systems that have been implicated in embryogenesis. Emphasis is placed on the insulin family of peptides, including insulin and the structurally and functionally related insulin-like growth factors. The initial chapters provide a review of basic topics, including developmental genetics, energy metabolism and hormonal signaling mechanisms, which are important prerequisites to the central theme that follows. The book concludes with a brief review of oncogene expression in early development; this new field has contributed significantly to our understanding of how mitogenic signals activate genetic elements responsible for embryonic growth and development. This book presents information important to cell biologists, endocrinologists, biological chemists, and developmental biologists.

Chapter 1

GENETICS OF EARLY MOUSE DEVELOPMENT

Lynn M. Wiley and Michael Femi Obasaju

TABLE OF CONTENTS

I. Introduction

A. Overview of Early Mouse Development

B. Major Questions Regarding the Genetic Aspects of Early Development

II. Onset Of Embryonic Gene Expression

III. Contributions of the Male and Female Gametes to the Embryo: Maternal/Paternal Non-Equivalency

A. Embryos Produced by Pronuclear Transfer

B. Embryos Produced by Natural Fertilization

C. Speculation on the Molecular Basis of Maternal/Paternal Non-Equivalency

IV. Cloning Mammals

A. Pluripotency of Mammalian Embryonic Nuclei

B. Pluripotency of Mammalian Embryonic Cells

V. Male and Female Gametes Contribute Different Heritable Cytoplasmic Components to the Embryo: Mitochondrial Inheritance

VI. Chimeras: Genetic Mosaics that Illustrate the Existence of Embryonic Biogenic Factors

A. Embryonal Carcinoma Stem Cells within Chimeras

B. Chimeras as Biodosimeters

C. Rescue: Lethality Circumvented by Development

VII. Retroviruses

VIII. Introduction of Foreign Material into the Embryo

I. INTRODUCTION

A. OVERVIEW OF EARLY MOUSE DEVELOPMENT

The eutherian mammalian embryo begins development following fertilization within the ampulla of the oviduct. As it travels down the oviduct, the embryo undergoes three to four reduction cleavages, during which the blastomeres become progressively smaller with each cleavage. After a characteristic number of reduction cleavages, the embryo undergoes a series of morphogenetic events that transform it from a solid sphere of cells into a blastocyst. These events usually overlap with the time during which the embryo enters the uterus but may occur after uterine entry. In some species, including the mouse, the embryo is a morula when it enters the uterus.

The blastocyst is a cystic structure, whose wall, the trophectoderm, develops from the outer blastomeres of the morula into a polarized transporting epithelium that encloses and maintains the blastocoele.^{1, 2, 3} The former inner blastomeres of the morula now comprise the inner cell mass (ICM), a cluster of cells that adhere to the inner surface of the trophectoderm. These first two cell types to evolve within the embryo synthesize cell-type-specific gene products that distinguish them from each other and from their shared blastomere progenitors. Neither trophectoderm nor ICM can resume the genetic repertoire of their progenitor blastomeres. Trophectoderm is the only tissue that can implement implantation and development of the placenta, while the ICM is the only tissue that can develop into the fetus.^4,5

In the uterus, the blastocyst expands, escapes from the zona pellucida, and proceeds to implant and develop additional epithelial layers and embryonic cavities that comprise the extraembryonic membranes, the placenta, and the definitive embryo. As these events proceed, they are accompanied by several genetic correlates. Some of these correlates are associated with the formation of the primary germ layers, while others are associated with whether a given cell finds itself a component of the embryo proper or of an extraembryonic membrane. In most cases, the functional rationales for these genetic correlates are not yet appreciated, and the belief that such rationales exist inspires much of the current research in mammalian development.

B. MAJOR QUESTIONS REGARDING THE GENETIC ASPECTS OF EARLY DEVELOPMENT

It is the purpose of this chapter to examine some of the major research questions now posed regarding these genetic correlates with respect to what they imply about developmental control. The questions we will examine here include (1) when does the embryonic genome become functional? (2) do male and female pronuclei make equivalent contributions to the embryo? (3) are the male and female genetic contributions expressed differentially within different tissues? (4) when do embryonic cells and embryonic nuclei lose their pluripotentiality? (5) do male and female gametes contribute equivalently to the embryo? and (6) what regulates cellular proliferation in the embryo?

This chapter, for the most part, will be limited to information obtained from the mouse embryo, simply because most of what we know about developmental genetics has been derived from studies on the mouse. However, where known, information pertaining to other species shall be included. The period of development surveyed in this chapter will extend from fertilization to the formation of the primitive streak, since most of current knowledge applies to this time period.

II. ONSET OF EMBRYONIC GENE EXPRESSION

Gamete fusion provides the embryo with several potential sources of messenger RNA (mRNA), namely, mRNA from the sperm cytoplasm and from the oocyte cytoplasm and newly transcribed mRNA from the embryonic genome. In the mammal, there is no evidence for sperm contributing translatable mRNA to the embryo. The oocyte, on the other hand, does contribute mRNA to the embryo, some of which is polyadenylated and, presumably, available for translation. In most metazoan species, maternal mRNA that is stored in the oocyte prior to fertilization controls the majority of protein synthesis up to gastrulation when germ layer formation begins.^{6, 7, 8} In mammalian embryos, however, proteins encoded by maternal mRNA virtually cease being synthesized prior to trophectoderm/ICM differentiation. In the mouse, maternal mRNA-encoded proteins are synthesized only into the two-cell stage, 25 to 28 h after fertilization,^9,10 after which the major portion becomes degraded.^{11, 12, 13} There is speculation, however, that some translatable maternal RNAs or additional unidentified cytoplasmic elements^14,15 persist longer during cleavage, because maternally inherited effects on development have been observed well beyond the two-cell stage.^{16, 17, 18}

Again, in contrast to most non-mammalian species, the first embryonic encoded mRNAs in the mouse embryo are detectable very early, some time during the first three cleavages, which is well before overt cell differentiation has occurred (Table 1). Interestingly, the onset of embryonic gene expression appears to correlate temporally with the spontaneous cleavage arrest many embryos undergo during development in vitro.^{19, 20, 21} Cultured one-cell mouse embryos from most strains will cleave once and no further (two-cell block), and the first embryonic mRNAs appear before the first cleavage in the mouse^{22, 23, 24, 25} with the corresponding proteins becoming detectable shortly after the first cleavage. Some of the proteins that appear initially in the two-cell mouse embryo include B₂-microglobulin²⁶ and B-glucuronidase.²⁷ With each successive cleavage, additional embryo-encoded gene products begin to appear, but the order of their appearance does not seem to follow any obvious relationship to coincident developmental events (Table 2).

...

TABLE 1
Onset of Embryonic Gene Expression in Different Mammalian Species

Species	Embyonic stage for initial appearance of embyonic proteins (time postovulation)	Length of gestation (days after fertilization)	Ref.
Mouse	2-cell stage (22—32 h)	19—20	19,26,27
Sheep	8-cell stage (37—48 h)	145—155	21
Pig	4-cell stage (1—3 d)	112—115	20
Human	4-8 cell stage (43—50 h)	252—274

Table of contents

• Cover
• Title Page
• Copyright Page
• Preface
• The Editors
• Contributors
• Dedication
• Table of Contents
• Chapter 1 Genetics of Early Mouse Development
• Chapter 2 Control of Carbohydrate Metabolism in Preimplantation Mammalian Embryos
• Chapter 3 Hormonal Signaling Mechanisms: The Role of Protein Phosphorylation in Early Development
• Chapter 4 Comparative Aspects of Insulin and the Insulin Receptor
• Chapter 5 Insulin and Insulin-Like Growth Factors (IGFs) in Avian Development
• Chapter 6 Insulin and Insulin-Like Growth Factors in Mammalian Development
• Chapter 7 Use of Embryonal Carcinoma Cells to Study Growth Factors During Early Mammalian Development
• Chapter 8 Growth Factor Signaling in Early Mammalian Development
• Chapter 9 The Expression of Oncogenes in Mammalian Embryogenesis
• Index