Biology Reference
In-Depth Information
5. FEEDFORWARD LOOPS DOWNSTREAM OF THE
TEMPORAL SEQUENCE CONTROL NEURON FATES
Some temporal genes are expressed in a broad temporal window, dur-
ing which multiple cell types are specified. How does a given temporal gene
control multiple cell fates? An elegant timing mechanism subdivides the
broad castor window in the NB5-6 lineage (
Baumgardt et al., 2009
). This
NB lineage (producing in total
20 progeny cells) ends with a broad castor
window, during which
10 cells are born, including the four last-born neu-
rons that express the LIM-homeodomain TF Apterous (Ap), designated the
Ap cluster (Ap1-4). The broad Cas window actually consists of two phases of
Cas expression with a brief interruption of Cas expression when the Ap1
neuron is born. Ap1 and Ap4 are peptidergic neurons expressing the Nplp1
and FMRFamide neuropeptides, respectively. Ap2 and Ap3 are interneu-
rons (
Baumgardt, Miguel-Aliaga, Karlsson, Ekman, & Thor, 2007;
Benveniste, Thor, Thomas, & Taghert, 1998; Park, Han, Kim, Han, &
Taghert, 2004
). The Ap cluster neurons are each born directly from a
NB without a GMC intermediate (
Baumgardt et al., 2009
). Cell fate diver-
sification of the four Ap neurons is achieved through three regulatory events
triggered by Cas: (1) Cas activates the COE class TF Collier/Knot (Col) in
the NB throughout the time Ap cluster neurons are born. It is initially
inherited in all four Ap neurons, but it is only maintained in Ap1 where
it acts in a feedforward loop involving sequential activation of Ap/Eyes
absent, Dimmed, and Nplp1 to specify this cell fate (
Baumgardt et al.,
2007
). (2) Cas also activates the zinc-finger protein squeeze (Sqz) in NBs,
which is maintained in all four Ap neurons. After Sqz had time to accumulate
in slightly later NBs, it acts with Cas to activate Nab, which is thus only
inherited in Ap2-4. Sqz and Nab together rapidly downregulate Col in
Ap2-4 neurons, and allow them to adopt fates different from Ap1
(
Baumgardt et al., 2009
). (3) Cas activates Grh expression, leading to gradual
increase of Grh levels. Grh is required for the specification of Ap4 (
Baumgardt
et al., 2009
). Thus, the broad Cas window is subdivided by these opposing
feedforward loops that ensure the generation of neurons with different iden-
tities (
Fig. 3.5
).
Similar regulatory logic might be widely used in other NB lineages to
increase neural diversity. In the NB3-3 lineage, Nab and Sqz also function
to specify temporal identities in the Cas window (
Tsuji et al., 2008
). In the
medulla, NBs are estimated to generate 2-6 GMCs at each temporal TF
