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generate ectopic U neurons (
Pearson & Doe, 2003
). Further studies showed
that NB7-1 has a single early competence window spanning the first five
divisions for responding to Hb, Kr, Pdm, or Cas to make the corresponding
U motor neurons. Then, NBs completely lose the competence to produce
U motor neurons in response to these TFs (
Cleary & Doe, 2006
;
Fig. 3.1
).
Similarly in the NB3-1 lineage, when the NB switches to generate interneu-
rons at the fifth division, the competence to generate RP3 motor neurons
in response to Kr is lost (
Tran & Doe, 2008
). This suggests that NBs can go
sequentially through several competence windows in which they respond
differently to the same temporal TF, allowing the repeated use of the same
TF within one lineage to specify different fates (
Cleary & Doe, 2006;
Pearson & Doe, 2003
).
The NB competence window can be extended if ectopic Hb is contin-
uously provided before endogenous Hb is downregulated. In this case,
NBs generate many U1/U2 neurons. They also retain their competence
to generate later-born U motor neurons, and the lineage is extended. Thus,
downregulation of Hb expression is required for the gradual loss of NB
competence to respond to Hb (
Cleary & Doe, 2006; Grosskortenhaus
et al., 2005; Isshiki et al., 2001
). Repression of multiple target genes (includ-
ing Pdm2) by sustained Hb is necessary and sufficient for the maintenance of
NB competence. Indeed, sustained expression of a form of Hb that functions
solely as a transcription activator cannot significantly extend the competence
window (
Tran, Miller, & Doe, 2010
).
Therefore, loss of NB competence to generate certain neuron fates lags
behind the progression of the TF sequence (e.g., for cell fate specified by
Hb, it is 3 cell divisions later) (
Kohwi, Lupton, Lai, Miller, & Doe, 2013;
Pearson & Doe, 2003
). However, progression of the TF sequence, that
is, downregulation of Hb relieving its transcription repression on multiple
target genes, including a later temporal TF (Pdm), is required for the NB
to close the current competence window and transit to the next.
4.3. Epigenetic mechanism for loss of NB competence
Recent studies uncovered a close relationship between epigenetic mecha-
nism and loss of NB competence. Mammalian cortical neural stem cells gen-
erate cortical neurons that populate the different layers, and then lose
the competence to generate neurons and switch to producing glia. This is
due to the Polycomb repressor complexes (PRCs) that are required to
suppress transcription of the neural fate TF neurogenin 1 in late-stage
