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progenitors (
Hirabayashi et al., 2009
). PRCs induce repressive chromatin
marks at the neurogenin 1 locus that gradually accumulate over time, and
thus may provide a timer for the loss of competence to make neurons
(
Hirabayashi et al., 2009
).
In
Drosophila
, PRCs are also involved in progressively restricting com-
petence for generating motor neurons in NB7-1 and NB3-1: PRC loss
of function extends the competence window to generate the corresponding
motor neuron fate in response to Kr, while PRC gain of function preco-
ciously restricts this competence. In contrast, PRC activity does not affect
the production of interneurons in multiple lineages (
Touma, Weckerle, &
Cleary, 2012
), suggesting that it is involved specifically in the repression of
multiple target genes involved in motor neuron specification (
Fig. 3.1
).
Chromosomal architecture has also recently been shown to be involved
in the loss of competence of NB7-1 to respond to Hb, three NB divisions
after
hb
transcription have stopped. At this stage, the
hb
gene locus relocates
to the nuclear periphery of the NB, a repressive subnuclear compartment,
preventing further activation of the
hb
gene by ectopic Hb, which is a
requirement for the specification of early-born neurons (
Kohwi et al.,
2013
;
Fig. 3.1
). The timing of the relocation correlates with downregulation
of the Pipsqueak domain nuclear protein, Dan. Prolonging the expression of
Dan can extend the NB competence by preventing relocalization of the
hb
locus at the periphery. This study proposed that Dan might competitively
inhibit other Pipsqueak-domain factors, for example, Pipsqueak, a GAGA-
binding factor essential for sequence-specific targeting of PRCs (
Huang,
Chang, Yang, Pan, & King, 2002
), from binding to and recruiting
hb
and
other loci to the nuclear lamina (
Kohwi et al., 2013
). This is consistent with
the model that PRCs are involved in restricting NB competence (
Touma
et al., 2012
).
In the medulla temporal sequence, NB competence has not yet been
well characterized. Although mis-expressing the first NB TF Hth in all
NBs leads to ectopic neurons with early-born cell fate, the phenotype
becomes less obvious in later part of the lineage, suggesting that the compe-
tence of NBs to generate early-born cell fate in response to the first NB TF
decreases with time. Whether the progressive loss of NB competence
involves similar epigenetic mechanism remains to be studied. Interestingly,
similar to the mammalian cortical neural stem cells, the medulla NBs switch
from neurogenic to gliogenic at their final temporal stage when they express
Tll (
Li et al., 2013
). Whether and how they lose the competence to generate
neurons at this stage awaits further study.
