ABSTRACT
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Three stages of development
The development of tissues in multicellular organisms requires three steps. (i) Individual cells must detect their position in the embryo by chemical cues from their surroundings, including contact with neighboring cells. (ii) The cells must respond to this by regulating their gene expression, and remember or lock the state epigenetically to control future development. (iii) The physical nature of the cells must change to fulfill their role in the organism. Understanding this process has come principally from looking at genetic mutants that do not develop properly, and looking at the expression of genes as mRNA or protein in developing embryos of insects (Drosophila), vertebrates (chicks, amphibians, mice), and nematodes (Caenorhabditis elegans).
Single cells to multicellular organisms
Single-celled bacteria (Bacillus) and yeasts differentiate to form dormant spores in adverse conditions. The slime molds (Dictyostelium) are free-living soil myxoamoebae reproducing asexually. When they reach a high density and use up the available nutrients, starved cells secrete pulses of cyclic adenosine monophosphate (cAMP) which signals surrounding amoebae to migrate into a clump which forms a multicellular grex that migrates and differentiates into stalk cells and spore cells.
Early Drosophila embryos
The main feature of development is that differentiation is controlled by transcription factors that regulate many other genes. Drosophila eggs are polarized by localization of maternal mRNAs from surrounding nurse cells localized in anterior/posterior and dorsal/ventral patterns. The relative concentrations of the proteins translated from these genes activate embryonic gap genes: Hunchback (anterior), Krüppell (middle), and Knirps (posterior), and others that specify cells as belonging to the main regions of the embryo. The overlaps of these gene products induces other genes in bands, and the process continues, activating pair-rule genes, until the familiar pattern of segmentation is produced, finalized by expression of segment polarity genes. The development of cells from each segment is further specified by Hox genes that indicate body position.
Homeobox genes (including Hox)
The structure of adult flies and vertebrates is controlled by homeobox genes which contain a conserved 180 bp DNA sequence coding 60 conserved amino acids (homeodomain). These are all transcription factors. One group occurs sequentially on the DNA and is expressed in a matching linear sequence, both anterior-posterior in the body and proximal-distal in the limbs. For example, mutations in Antennapedia cause small legs to grow from the head where the antennae should be. This type of homeotic change (one structure replacing another) gave the name to the class of genes. Gene mapping and DNA sequencing revealed a cluster (now called Hox genes) of these genes resulting from tandem duplications of ancestral genes, followed by diversification and specialization. The same clustered family of genes exists in all metazoans but most vertebrates have four complete sets containing 39 genes in total. Teleost fish have seven sets. Individual genes may be lost or duplicated in individual clusters.
All metazoans including vertebrates use the same developmental genes
The current evidence is that the same signaling molecules and responding transcription factors are used in the same regions of the embryo in all species. The same Hox genes in different tissues produce different effects. There are evolutionary differences in exact timing and duration of individual stages and in the final genes that are regulated, which give the differences in body form of different animals, including vertebrates. Examination of large, free eggs of fish and amphibians, and detection of RNA and protein in microscopy sections of mouse embryos confirm a common set of developmental genes in all metazoans.
Globins as a developmentally regulated gene
The globin genes occur as an α cluster containing ζ, α 1, and α 2 genes, and a β globin cluster containing ε, Gγ, Aγ, γ, and β genes. These are controlled by a large upstream locus control region (LCR) which moves along the cluster during embryo development switching genes on as it reaches them and off as it passes, regulating sequential transcription.
Caenorhabditis elegans development
Caenorhabditis elegans is a nematode used extensively as a model genetic organism. Although it has a similar toolkit of developmental genes to other animals, it has a profoundly different developmental mechanism. The fate of each cell is controlled by its lineage.
Programmed cell death
Cell death by apoptosis is an essential part of development and is genetically programmed. One example is the loss of cells between the fingers and toes. Their persistence leads to webbing, as seen in ducks' feet.
Plants have similar mechanisms to animals
Plants also have developmental genes, including homeobox genes, although most plant developmental genes are MADS box genes. Plants appear to rely on diffusible paracrine inducers. In general plants are less well studied than animals.
Related topics
Regulation of gene expression
Epigenetics and chromatin modification
