10.4: Differentiation

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Complex multicellular organisms undergo a process known as embryonic development319. Development begins with the fusion of a haploid sperm and egg (produced through meiosis) to form a new diploid organism (known as zygote). This cell then divides (by mitosis) to produce an embryo that develops into an adult. Cell division leads to embryonic cells that begin to behave differently from one another. For example, while the original diploid cell generated by fertilization is totipotent - that is, it can generate all of the cells found in the adult, the cells formed during development become more and more restricted with respect to the types of progeny that they produce–they become committed to one or another specific fate. In part this fate restriction is due to the fact that as cells divide, different cells come to have different neighbors and they experience different environments, leading to the expression of different genes. The question becomes, what determines what types of cells an embryonic (increasingly differentiated) cell produce?

There are two basic, and interacting, processes that drive embryonic development. During the formation of the egg and following fertilization, cytoplasmic determinants (which may be proteins, RNAs, or metabolic products) can become localized to, or active in, specific regions of the egg, and later to specific regions of the embryo. The presence of these cytoplasmic determinants drives the cell that contains them in specific developmental directions based on changes in gene expression. At the same time, there are changing interactions between cells and cells come to inhabit different environments. Together asymmetries and interactions lead cels to express different genes and to adopt specific fates. There are many different types of embryonic development, since this stage of an organism’s life cycle is as subject to the effects of evolutionary pressures as any other (although it is easy to concentrate our attentions on adult forms and behaviors). The study of these processes, known as embryology, is beyond our scope here, but we can outline a few common themes.

If fertilized eggs develop outside of the body of the mother and without parental protection, these new organisms are highly vulnerable to predation. In such organisms, early embryonic development generally proceeds rapidly. The eggs are large and contain all of the nutrients required for development to proceed up to the point where the new organism can feed on its own. To facilitate such rapid development, the egg is essentially pre-organized, that is, it is highly asymmetric, with specific factors that can influence gene expression, either directly or indirectly, positioned in various regions of the egg. Entry of the sperm (the male gamete), which itself is an inherently asymmetric process, can also lead to reorganization of the cytoplasm (SEP marks sperm entry point in the figure early frog development). Maternal and fertilization-driven asymmetries are stabilized by the rapid cycles of DNA replication and cell division, with growth being dependent upon the utilization of maternally supplied nutrients. As distinct cells are formed, they begin to become different from one another as i) they inherit different determinants, ii) the presence of these determinants leads to changes in gene expression, and iii) cells secrete and respond to different factors that drive their differentiation further into different cell types, with different behaviors based on differences in gene expression.

On the other hand, in a number of organisms, and specifically mammals, embryonic development occurs within the mother, so there is no compelling need to stockpile nutrients within the egg and the rate of development is (generally) dramatically slower. In such developmental systems, it is not the asymmetries associated with the oocyte and fertilized egg that are critical, but rather the asymmetries that arise during embryonic development. As the zygote divides, a major factor that drives the differentiation is whether a cell comes to lie on the surface of the embryo or within the interior. In mammals, the cells on the exterior form the trophectoderm, which goes on to form extraembryonic tissues, in particular the membranous tissues that surround the embryo and become part of the placenta, the interface between the embryo and the mother. Cells within the interior form the inner cell mass that produces to the embryo proper. Changes in gene expression will lead to changes in the ability to produce and respond to inductive signals, which will in turn influence cell behavior and gene expression. Through this process, the cells of the inner cell mass come to form the various tissues and organs of the organism; that is, skin, muscle, nerve, hair, bone,blood, etc. It is easy to tell a muscle cell from a neuron from a bone cell from a skin cell by the set of genes they express, the proteins they contain, their shapes (morphology), their internal organization, and their behaviors.