Cell diversification does not always have to depend on extracellular signals: in some cases, sister cells are born different as a result of an asymmetric cell division, during which some significant set of molecules is divided unequally between them. This asymmetrically segregated molecule (or set of molecules) then acts as a determinant for one of the cell fates by directly or indirectly altering the pattern of gene expression within the daughter cell that receives it (see Figure 21–12). We have already encountered the asymmetric segregation of molecules in the context of the early frog embryo: VegT RNA is localized in the vegetal region of the fertilized egg. Following cell division, only vegetal daughter cells will inherit VegT RNA.
Asymmetric divisions often occur at the beginning of development, but they are also encountered at some later stages. As mentioned for the sensory bristle, they can set the scene for an exchange of Notch signals between the daughter cells, with the signaling occurring after the cells have become separate and reinforcing the differences between them. In the central nervous system, asymmetric divisions have a key role in generating the very large numbers of neurons and glial cells that are needed. A special class of cells becomes committed as neural precursors, but instead of differentiating directly as neurons or glial cells, these undergo a long series of asymmetric divisions through which a succession of additional neurons and glial cells are added to the population. The process is best understood in Drosophila, although there are many hints that something similar occurs also in vertebrate neurogenesis.
In the embryonic central nervous system of Drosophila, the nerve-cell precursors, or neuroblasts, are initially singled out from the neurogenic ectoderm by a typical lateral-inhibition mechanism that depends on Notch. Each neuroblast then divides repeatedly in an asymmetric fashion (Figure 21–36). At each division, one daughter remains as a neuroblast, while the other, which is much
Figure 21–35 Lateral inhibition. (a) the basic mechanism of Notch-mediated competitive lateral inhibition, illustrated for just two interacting cells. In this diagram, the absence of color on proteins or effector lines indicates inactivity. (B) the outcome of the same process operating in a larger patch of cells. at first, all cells in the patch are equivalent, expressing both the transmembrane receptor Notch and its transmembrane ligand Delta. each cell has a tendency to specialize (as a sensory mother cell), and each sends an inhibitory signal to its neighbors to discourage them from also specializing in that way. this creates a competitive situation. as soon as an individual cell gains any advantage in the competition, that advantage becomes magnified. the winning cell, as it becomes more strongly committed to differentiating as a sensory mother cell, also inhibits its neighbors more strongly. conversely, as these neighbors lose their capacity to differentiate as sensory mothers, they also lose their capacity to inhibit other cells from doing so. Lateral inhibition thus makes adjacent cells follow different fates.
although the interaction is thought to be normally dependent on cell–cell contacts, the future sensory mother cell may be able to deliver an inhibitory signal to cells that are more than one cell diameter away—for example, by sending out long protrusions to touch them.
smaller, becomes specialized as a ganglion mother cell. Each ganglion mother cell will divide only once, giving a pair of neurons, or a neuron plus a glial cell, or a pair of glial cells, with Notch-mediated interactions helping to drive the daughters along different paths. The neuroblast itself becomes smaller at each division, as it parcels out its substance into one ganglion mother cell after another. Eventually, typically after about 12 cycles, the process halts, presumably because the neuroblast becomes too small to pass the cell-size checkpoint in the cell-division cycle. Later, in the larva, neuroblast divisions resume, but now they are accompanied by cell growth, permitting the process to continue indefinitely and to generate the much larger numbers of neurons and glial cells required in the adult fly.