Development

I

Introduction

Development, the change of form of living organisms with time. The subject of developmental biology is specifically devoted to this topic. Development represents an entirely separate problem from the change of form that occurs in lines of descent during evolutionary time, although an understanding of individual development is necessary for a proper understanding of the genetic basis of evolutionary change. Development is mainly found in multicellular organisms but there are also some developmental phenomena in the larger and more complex types of single-celled organisms, such as ciliates.

In animals, changes of form with time occur chiefly during embryonic development from eggs, but there are also developmental changes found in postembryonic life, namely growth, metamorphosis, asexual reproduction, and regeneration. In higher plants, development is more obviously continuous, occurring at the growing points (meristems) of roots and shoots.

An organism consists of a number of distinct parts. Animals usually have their parts arranged in a particular way to form a recognizable anatomy for each animal species. The parts are assembled from a number of different types of cell; for example animals usually possess skin, nerve, muscle, gland, and absorptive epithelia; while plants possess epidermal, parencymal, and vascular tissues. Different cell types differ from each other because a different subset of genes from the organism’s genome is expressed, and hence a different subset of proteins is present and active.

The essence of development, which applies to both plants and animals, is that a sheet of cells becomes divided up into smaller regions, each of which later forms a particular cell type or set of cell types constituting one body part. This process is called regional specification. At the time when it occurs, all the cells of the sheet still look the same down the microscope, but in each of the new regions a different combination of special regulatory genes that control development is turned on. These genes are known as homeotic, or selector, genes, and they code for a type of protein called transcription factors, that can regulate the expression of many other genes by binding to nearby regions of DNA and activating or repressing their expression.

All multicellular animals are subdivided into a number of regions from the head to the tail by means of a particular set of these homeotic genes, known as the HOX genes. In each region a different combination of the HOX genes is active. The fact that similar genes control the head to tail pattern of animals as diverse as a flatworm and a human strongly suggests that all animals must have had a common evolutionary ancestor at some remote time in the past. Plants do not share this feature, but the parts of the flowers of higher plants are coded in a comparable way by a different set of selector genes called the MADS genes.

During development, each homeotic gene become activated in the appropriate position within the embryo by chemical signals called inducing factors. Because the identity of a part of the organism depends on the combination of homeotic genes that is expressed there, mutations in these genes bring about changes in the combinations expressed and this can change one part of the body into another. A well-known example is the change from two to four in the number of wings in the fruit fly Drosophila, by inactivation of the gene called Ultrabithorax. Homeotic mutations occur naturally in some insects and plants and can also be produced experimentally in vertebrates.

Development from egg to adult will normally involve several rounds of regional specification. Initially a few large subdivisions are created. Each of these later becomes subdivided, and subdivision continues until the final body complexity has been achieved. (See also Evolutionary Developmental Biology.)

II

The Egg

An egg (or ovum) is a female reproductive cell, or gamete. It has the ability to develop into a new organism after fertilization by a sperm, which is the male gamete. In animals, the sexes are normally separate and the eggs are formed in the female in a process known as oogenesis. Plants are usually hermaphrodite and the same flower can form both pollen and eggs.

Sexually reproducing organisms are, for at least part of their life cycle, diploid, which means that they carry two complete sets of genes, one from each parent. Cells that contain only one gene set are said to be haploid. The process of sexual reproduction involves the halving of the genome such that haploid gametes are formed, followed by the union of egg and sperm (fertilization) to produce a fertilized egg, or zygote, with the diploid condition restored. The type of cell division in which the genome is halved is called meiosis. In animals this occurs only during gamete formation, while in some lower plants such as ferns, meiosis may give rise to a haploid stage of the life cycle called a gametophyte, which subsequently produces sexual gametes.

A female germ cell is initially called an oogonium. After their final mitosis, the oogonia become oocytes. DNA replication occurs as normal and then the oocyte undergoes a long growth period during which it remains arrested at the beginning of meiosis. Meiosis finally proceeds on receipt of an appropriate hormonal stimulus and the oocyte matures into an ovum, or unfertilized egg. Since the oocyte is a diploid cell that has undergone DNA replication, it contains four copies of each gene, so three copies are surplus to requirements for the formation of a single haploid egg. During maturation, the nucleus, known as the germinal vesicle, breaks down, and the unwanted chromosome sets are expelled as the first (diploid) and second (haploid) polar bodies, leaving the egg with all the cytoplasm and one haploid chromosome set. Following fertilization, the ovum becomes a fertilized egg or zygote. Embryos in the early stages of cell division are also sometimes referred to as eggs, although this is strictly incorrect.

Apart from providing a haploid genome, the egg has two other important tasks to perform. First, it contains the initial food supply that sustains the developing embryo until it has access to an external source of nutrients. This may be a rather short time, as in mammalian reproduction where eggs are small and implant into the maternal uterus at an early stage of embryonic development; or it may be a long time, as most obviously seen in birds, which have large eggs containing an abundant food supply. Secondly, the egg must have some internal subdivision in order to initiate the process of regional specification in the developing embryo. This is achieved by localizing substances called determinants to particular parts of the egg. When the egg has divided up to form a multicellular embryo, a homeotic gene may be specifically activated or repressed only in those cells containing the determinant and not in other parts of the embryo.

The process of oogenesis has been studied in detail in the fruit fly Drosophila. The germ cells are formed very early in development and somewhat later they migrate to the developing gonads to become oogonia. At a critical stage, an oogonium divides four times to form a cluster of 16 cells. One of these becomes an oocyte and the other 15 become nurse cells. The 16 cells are surrounded by somatic, nongerm line, cells called follicle cells. The food reserves of the oocyte are built up in three ways. First, some materials, such as the yolk proteins, are synthesized in the fat body of the fly and in other parts of the ovary, and are later absorbed from the blood (haemolymph) by the oocyte. Secondly, other materials such as ribosomes, are synthesized in the nurse cells and passed into the oocyte through cytoplasmic bridges. Thirdly, certain gene products are also synthesized by the oocyte itself. As a result of these processes the oocyte becomes much larger than the nurse cells and is able to sustain development of the embryo to the feeding larva stage. The frog oocyte is also quite well studied. In the frog there are no nurse cells but the oocyte also absorbs yolk and other materials from the blood as it grows.

The second essential function of the egg involves initiating the sequence of regional subdivisions into different cell types that occurs during embryonic development. In Drosophila there are four known determinants. Two are composed of messenger RNAs located respectively around the head and the tail end of the egg. The remaining two are the active forms of cell surface receptors—proteins located in the plasma membrane—capable of binding and responding to inducing factors. One of these is activated on the ventral side of the egg and the other at the egg termini, in both cases in response to inducing factors released by the adjacent follicle cells. In the frog embryo, several mRNAs are located around the lower half of the egg, including at least one coding for a mesoderm-inducing factor.

III

Embryonic Development of Animals

Regional specification is the central process of development but, in animals, cell movements are also very important. Contrary to general belief, growth is not a necessary feature of embryonic development in animals. This is because most animals develop from free-living eggs with no external food supply. They cannot grow until the larva is able to feed, so development is accompanied by a reduction of dry weight even if the volume of the organism increases by uptake of water. Animal development typically starts with cleavage, when the egg divides many times to form a ball of cells called a blastula. This is followed by a phase of cell movements called gastrulation during which a three-layered body structure is formed. The outer layer is known as ectoderm, the middle layer is the mesoderm, and the inner layer is the endoderm. The general body plan of the animal group to which the embryo belongs finally becomes visible at the phylotypic stage. It is at this stage that the HOX genes controlling the head-to-tail pattern are most actively expressed.

IV

Regional Specification and Induction

Regional specification means the commitment of cells or groups of cells to form particular parts of the body. These may correspond to the later organs, or may be broader domains such as “anterior”, “middle”, and “posterior”. The first steps of regional specification are brought about by determinants in the egg, either deposited during oogenesis, or at the time of fertilization. All types of animal egg probably contain determinants, although the molecular basis is best understood for the fruit fly Drosophila, as mentioned above.

After the determinants have done their job, subsequent regional specification occurs by the process of embryonic induction; whereby one group of cells can control the development of another group by the emission of a chemical signal, or inducing factor. One set of genes is turned on in those target cells exposed to more than a critical concentration of the factor, while a different set become turned on in the cells exposed to lower concentrations. So the target cells exposed to the high concentration form one cell type and those exposed to the lower concentration form another. Hence induction increases the spatial complexity of the embryo by subdividing groups of cells into two or more regions, each specified to become a different structure or cell type.

Recent progress in the identification of inducing factors has shown that many of them are the same substances that have been known as growth factors in the context of animal tissue culture. Growth factors work by stimulating specific cell surface receptors—proteins located in the plasma membrane of the responding cells. Receptor molecules have a factor-binding domain on the outside of the cell and an enzymic site on the inside that is activated by binding of the factor. The sequence of metabolic changes initiated by the activated receptor eventually leads to the activation or repression of specific genes, and hence the formation of a new cell type. Although each inductive step only produces one or a few new cell types, a succession of interactions can rapidly produce a high degree of morphological complexity.

In the frog embryo the first important inductive interaction occurs at the blastula stage, when the embryo consists of a simple ball of cells. The cells of the lower (vegetal) hemisphere emit mesoderm-inducing factors that cause the belt of cells lying around the equator of the blastula to become mesodermal in character by the activation of specific genes. The remainder of the animal hemisphere, out of range of the signal, becomes ectodermal. During the gastrulation phase, further inductions occur in which the different tissues within the mesoderm are formed (dorsalization) and the neural plate becomes induced from the ectoderm (neuralization). In later development there are numerous local inductive interactions concerned with the formation and maturation of the individual organs. Although the development of the frog is better understood than that of other vertebrates, it is likely that the general course of inductive signals and responses is similar in mammals, birds, reptiles, and fish.