Project Details
Abstract
Neurogenesis requires precise control of gene transcription. The bHLH
proneural proteins are highly conserved transcriptional activators, and play key roles
in neurogenesis from fly to human. In Drosophila, the proneural proteins Achaetae
(Ac) and Scute (Sc) promote external sensory (ES) organ formation through
transcriptional activation. Previous study in our lab showed that actin, the major
component of the cytoskeleton, associates with Ac and Sc in nucleus and is required
for Ac and Sc to activate transcription. In addition to actin, we recently discovered
that the actin-related protein 6 (Arp6), a member of the actin family protein, associate
with Ac and Sc in Drosophila cells. Arp6 is highly conserved from yeast to human,
and studies of yeast and human Arp6 show that it is primarily localized in nucleus.
We also found that it is Arp6, but not other nuclear Arps including Arp4, Arp5 and
Arp8, associates with proneural proteins. Analysis of Arp6 loss-of-function knock-in
allele generated by CRISPER/Cas9 showed that Arp6 is required for timely high-level
Ac expression in sensory organ precursors (SOPs). Results from yeast and plant show
that Arp6 is a component of SWR1 chromatin remodeling complex that is required for
H2Av variant exchange in the nucleosome. In this grant, we propose to study whether
Arp6 promotes high-level Ac auto-regulation in SOPs through H2Av and the SWR1
ATPase Domino. Our study in S2 cells also showed that Arp6 stabilizes Ac protein.
We will also explore the possible role of Arp6 in regulation of proneural protein
stability.
The ES organs on the fly notum, especially the microchaetae, are arranged in
rows in a precise pattern. Notch pathway is required for ES organ patterning through
both the cell contact-dependent Notch signaling, and the filopodia-mediated longrange
Notch signaling. In Arp6 mutant, the microchaetal density was increased,
suggesting that Arp6 is required for the long-range lateral inhibition transducing
through the filopodia. In addition, Arp6 is also required for wing margin formation, a
process mediated by the Notch pathway. In the second part of this grant, we propose
to investigate the mechanism of Arp6 and H2Av in filopodia-mediated lateral
inhibition and in Notch signaling.
Project IDs
Project ID:PA10501-1463
External Project ID:MOST104-2311-B182-004-MY3
External Project ID:MOST104-2311-B182-004-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/16 → 31/07/17 |
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