Scott Gilbert - Developmental Biology - 2010

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Created: October 28, 2017 / Updated: December 1, 2017 / Status: in progress / 8 min read (~1453 words)

  • The reason that cells do different things with the DNA is that they are similar to the disk and disk player of Godel, Escher, Bach, in the sense that the cell is itself a program that can consume the DNA (data), but is only interested in specific parts of it

  • One of the critical differences between you and a machine is that a machine is never required to function until after it is built
  • Every animal has to function even as it builds itself

  • There are two fundamental questions in developmental biology:
    • How does the fertilized egg give rise to the adult body?
    • How does that adult body produce yet another body?
  • Seven general categories of questions scrutinized by developmental biologists:
    • Differentiation: How can an identical set of genetic instructions produce different types of cells?
    • Morphogenesis: How can the cells in our body organize themselves into functional structures?
    • Growth: How do our cells know when to stop dividing? How is cell division so tightly regulated?
    • Reproduction: How are these germ cells (sperm and egg) set apart from the cells that are constructing the physical structures of the embryo, and what are the instructions in the nucleus and cytoplasm that allow them to form the next generation?
    • Regeneration: How do the stem cells retain their capacity (to form new structures even in adults), and can we harness it to cure debilitating diseases?
    • Evolution: How do changes in development create new body forms? Which heritable changes are possible, given the constraints imposed by the necessity that the organism survive as it develops?
    • Environmental integration: How is the development of an organism integrated into the larger context of its habitat?

  • Multicellular organisms do not spring forth fully formed. Rather, they arise by a relatively slow process of progressive change that we can development
  • In nearly all cases, the development of a multicellular organism begins with a single cell - the fertilized egg, or zygote, which divides mitotically to produce all the cells of the body

  • The stages of development between fertilization and hatching are collectively called embryogenesis
  • Six fundamental processes
    • Fertilization: Fusion of the mature sex cells, the sperm and the egg, which are collectively called the gametes. The fusion of the gamete nuclei gives the embryo its genome, the collection of genes that helps instruct the embryo to develop in a manner very similar to that of its parents
    • Cleavage: A series of extremely rapid mitotic divisions that immediately follow fertilization
    • Gastrulation: After the rate of mitotic slows down, the blastomeres underogo dramatic movements and change their positions relative to one another. As a result of gastrulation, the embryo contains three germ layers that will interact to generate the organs of the body
    • Organogenesis: The cells interact with one another and rearrange themselves to produce tissues and organs
    • Metamorphosis: To become a sexually mature adult
    • Gametogenesis: The development of gametes
  • The gametes and their precursor cells are collectively called germ cells (the formation of a new generation)
  • All other cells of the body are called somatic cells (the individual body)
  • The most important things to remember about meiosis are:
    • The chromosomes replicate prior to cell division, so that each gene is represented four times
    • The replicated chromosomes (each called a chromatid) are held together by their kinetochores (centromeres), and the four homologous chromatids pair together
    • The first meiotic division separates the chromatid pairs from one another
    • The second meiotic division splits the kinetochore such that each chromatid becomes a chromosome
    • The result is four germ cells, each with a haploid nucleus

  • von Baer's laws
    • The general features of a large group of animals appear earlier in development than do the specialized features of a smaller group
    • Less general characters develop from the more general, until finally the most specialized appear
    • The embryo of a given species, instead of passing through the adult stages of lower animals, departs more and more from them
    • Therefore, the early embryo of a higher animal is never like a lower animal, but only like its early embryo

  • One of the most important conclusions of developmental anatomists is that embryonic cells do not remain in one place, nor do they keep the same shape
  • Two major types of cells in the embryo:
    • Epithelial cells, which are tightly connected to one another in sheets or tubes
    • Mesenchymal cells, which are unconnected to one another and operate as independent units
  • Morphogenesis is brought about through a limited repertoire of variations in cellular processes within these two types of arrangements
    • Direction and number of cell divisions
    • Cell shape changes
    • Cell movement
    • Cell growth
    • Cell death
    • Changes in the composition of the cell membrane or secreted products
  • Given such a dynamic situation, one of the most important programs of descriptive biology became the tracing of cell lineages: following individual cells to see what those cells become
  • Vital dyes stain cells but do not kill them
  • One problem with vital dyes is that as they become more diluted with each cell division, they become difficult to detect
    • One way around this is to use fluorescent dyes that are so intense that once injected into individual cells, they can still be detected in the progeny of these cells many divisions later
  • In most animals, it is difficult to meld a chimera from two species. One way of circumventing this problem is to transplant cells from a genetically modified organism. In such technique, the genetic modification can then be traced only to those cells that express it
    • One version is to infect the cells of an embryo with a virus whose genes have been altered such that they express the gene for a fluorescently active protein such as GFP (green fluorescent protein)

  • Darwin argued that adaptations that depart from the "type" and allow an organism to survive in its particular environment develop late in the embryo
  • One of the most important distinctions made by evolutionary embryologists was the difference between analogy and homology
  • Both terms refer to the structures that appear to be similar
  • Homologous structures are those organs whose underlying similarity arises from their being derived from a common ancestral structure
  • Analogous structures are those whose similarity comes from their performing similar function rather than their arising from a common ancestor

  • Abnormalities caused by exogenous agents (certain chemicals or viruses, radiation, or hyperthermia) are called disruptions
  • The agents responsible for these disruptions are called teratogens, and the study of how environmental agents disrupt normal development is called teratology

  • How can nuclear genes direct development when these genes are the same in every cell type?
  • Three postulates of differential gene expression
    • Every cell nucleus contains the complete genome established in the fertilized egg. In molecular term, the DNAs of all differentiated cells are identical
    • The unused genes in differentiated cells are neither destroyed nor mutated, but retain the potential for being expressed
    • Only a small percentage of the genome is expressed in each cell, and a portion of the RNA synthesized in each cell is specific for that cell type
  • Gene expression can be regulated at several levels such that different cell types synthesize different sets of proteins
    • Differential gene transcription
    • Selective nuclear RNA processing
    • Selective messenger RNA translation
    • Differential protein modification

  • One of the fundamental differences distinguishing most eukaryotic genes from prokaryotic genes is that eukaryotic genes are contained within a complex of DNA and protein called chromatin
  • The nucleosome is the basic unit of chromatin structure
    • It is composed of an octamer of histone proteins
  • It is generally thought that the "default" condition of chromatin is a repressed state, and that tissue-specific genes become activated by local interruption of this repression
  • The histones are critical because they are responsible for maintaining the repression of gene expression
  • Repression and activation are controlled to a large extent by modifying the tails of histones H3 and H4 with two small organic groups: methyl and acetyl residues
  • The second difference between prokaryotic and eukaryotic genes is that eukaryotic genes are not co-linear with their peptide products. Rather, the single nucleic acid strand of eukaryotic mRNA comes from noncontiguous regions on the chromosome
  • Promoters are the sites where RNA polymerase binds to the DNA to initiate transcription