Biology Reference
In-Depth Information
In the medulla NB TF sequence, both Slp and D are required to turn off
the preceding TF and turn on the next TF, therefore, acting as switching
factors for themselves. Additional transition factors remain to be identified
for other transitions (
Li et al., 2013; Suzuki et al., 2013
).
4. RELATIONSHIP BETWEEN TEMPORAL SEQUENCE
AND NB COMPETENCE
4.1. Restriction of NB competence
Early studies in mammalian neurogenesis have demonstrated that neural
stem cells undergo progressive restriction in their competence to generate
different types of progeny in response to extrinsic signals (
Desai &
McConnell, 2000; Livesey & Cepko, 2001
). For example, during develop-
ment of the cerebral cortex, neural stem cells generate neurons in the six
cortical layers in an “inside-out” defined order, in which layer 6 and 5
neurons are generated first, followed by layer 4, 3 and 2. The fate of the
progeny also depends on environmental cues to which the cells respond
prior to cell division. Transplantation experiments showed that mid-stage
neural stem cells that are producing layer 4 neurons have the competence
to generate layer 2/3 (later-born) neurons when transplanted into older
brains. However, when these neural stem cells are transplanted into younger
brains in which layer 6 neurons are being generated, they have lost the com-
petence to generate layer 6 neurons. Instead, they produce layer 4 and 5 neu-
rons. Thus, the competence of neural stem cells to generate a given cell type
is progressively lost, although this loss of competence lags behinds the com-
pletion of generation of this neural type (
Desai & McConnell, 2000
).
4.2. TF sequence and regulation of NB competence
Loss of competence is also observed in
Drosophila
NBs, although, in this case,
competence responds to intrinsic TFs rather than extrinsic cues. In the
VNC, providing ectopic Hb to the NB after Hb has been downregulated
is sufficient to generate additional early-born neurons. However, this com-
petence to respond to Hb progressively decreases over time. In the NB7-1
lineage, a pulse of ectopic Hb at the time U1 and U2 are normally born leads
to the generation of several ectopic U1 and U2 neurons. If the pulse of
ectopic Hb is provided later, when U3 and U4 are normally born, only
one ectopic U2 neuron can be generated; and if Hb is given after the fifth
division when the NB switches to generate interneurons, the NB fails to
