Biology Reference
In-Depth Information
repress Grh. Thus, a “feedforward activation/feedback repression” model
for D
Ey cross-regulation appears to control the transitions of
TFs (
Bayraktar & Doe, 2013
;
Fig. 3.4
).
Considering the three know sequences of TFs in the VNC, medulla and
type II NBs, it is clear that a cross-regulatory network among the temporally
expressed TFs does have important roles in the transition between TFs.
However, more factors or timing mechanisms must be involved and may
vary case by case. Redundant mechanisms might also be present to ensure
the robustness of transitions.
!
Grh
!
3.2. Differential requirements for cell cycle and asymmetric
division
Since the NB progresses through the TF sequence as it undergoes asymmet-
ric divisions to produce neuronal progeny, cell cycle and cell division might
play a role in these transitions, either by cell-cycle dependent signaling
event, asymmetric localization of certain mRNA or protein, or by feedback
signal from the progeny. Indeed, the first Hb to Kr transition requires cell
cycle and cytokinesis, but it does not require asymmetric localization of
hb
mRNA or Hb protein. However, the Kr
Cas transitions are
regulated in a cell-cycle independent manner, and progress normally in
cell-cycle arrested NBs (
Grosskortenhaus et al., 2005
).
!
Pdm
!
3.3. Switching factors involved in TF transitions
As discussed above, Hb expression is downregulated at the transcription
level in a cell-division dependent manner (
Grosskortenhaus et al., 2005;
Kanai, Okabe, & Hiromi, 2005; Kohwi, Hiebert, & Doe, 2011; Mettler,
Vogler, & Urban, 2006
). The orphan nuclear receptor TF Svp is required
for the Hb to Kr switch in several NB lineages of the
Drosophila
embryonic
CNS (
Kanai et al., 2005
). Loss of
svp
causes prolonged Hb expression in NBs
as well as ectopic early-born neurons. The nuclear export of
svp
mRNA (and
thus its efficient translation) is dependent on the cell cycle (
Mettler et al.,
2006
), providing an explanation for the requirement of cell division for
the Hb to Kr transition.
In addition to Svp, the nuclear proteins distal antenna and distal antenna-
related proteins (Dan and Dan-r) function in parallel pathways with Svp to
downregulate Hb expression, and ensure the timely transition of the NBs
from making early-born neurons to generating late-born neurons (
Kohwi
et al., 2011
).
