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The expression of both spatial and temporal coor-
dinate genes in neuroblasts is preserved in their
progeny, the GMCs, and forms part of the increasingly
rich inheritance of each developing neural progenitor.
The ontogenetic roots of a neural progenitor can be
read in the combination of transcription factors it
expresses, and these factors in turn influence the cell's
eventual phenotype.
Both Prospero and Numb are initially present
throughout the entire neuroblast, so how do they get
asymmetrically segregated? Figure 4.6 shows how this
happens. Two proteins called Inscuteable (Insc) and
Bazooka (Baz) form a complex, the Insc complex, that
somehow recognizes and attaches to apical membrane
of the neuroblast. The Insc complex orients the mitotic
spindle along the apicobasal axis by anchoring the cen-
trioles, which results in a vertical mitotic spindle. At the
same time, the Insc complex, in conjunction with an
actin-based cytoskeleton mechanism, drives the distri-
bution of several key proteins along this vertical plane
so they are inherited asymmetrically (Kaltschmidt and
Brand, 2002). In particular, a cytoplasmic protein,
Miranda (Mira) becomes enriched at the basal neurob-
last pole such that when the cytokinesis separates
the neuroblast's daughter cells, Mira is trapped in the
GMC. It is Mira that binds the aforementioned deter-
minants, Numb and Prospero, to the basal neuroblast
pole and thus directs their localization to the GMC. The
more apical cell does not differentiate into a GMC;
rather it remains a neuroblast capable upon production
of more Mira, Prospero, and Numb, to spit off another
GMC at the next division. An example of the Numb
protein segregating to a single daughter is shown in
Figure 4.7.
An interesting example of a situation in which
daughter cells adopt different fates due to asymmetric
inheritance of Numb are the small sensory organs
called sensilla, scattered over the body surface in
Drosophila . The cells that compose each sensillum are
usually clonal descendants of a single sensory organ
precursor, SOP. The SOP cells are a bit like the neuro-
blasts that give rise to the CNS; they originally delam-
inate from the ectoderm during development in much
the same way, dependent on proneural genes and
Notch and Delta interactions, as described in Chapter
Typically, the progeny of a cell division inherit the
spatial and temporal coordinates expressed by the
parental neuroblast at the time of birth. However,
the parent cell often divides asymmetrically, giving
intrinsic determinants to one daughter but not the
other. As soon as they leave the neurectoderm behind,
insect neuroblasts start dividing asymmetrically to
produce two unequally sized daughter cells, a large
second-order neuroblast remaining at the surface and
the smaller GMC lying interiorly. How does a cell
accomplish the partitioning of information selectively
to one offspring and not the other? Two factors, Numb
and Prospero ( Pro ), are expressed in most neuroblasts
and are critical for asymmetric distribution of deter-
minants of cell identity. At neuroblast division, these
factors become localized to the smaller daughter, the
GMC, where Prospero moves into the nucleus and
positively influences GMC fate (Lu et al., 2000). Numb
acts by inhibiting the Notch signaling pathway by
binding to Notch and inactivating the transmission of
a signal to the nucleus (Chapter 1). In the absence of
Notch signaling, the GMC is free to move down the
determination pathway.
FIGURE 4.6 Control of asymmetrical cell division in Drosophila . The Inscuteable complex is localized to
the apical pole of the neuroblast where it orients the mitotic spindle and causes the basal localization of asym-
metrically localized determinants such as Miranda and Numb.
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