Functions of COP9 Signalosome and Nuclear Actin in Drosophila Sensory Organ Development: from Patterning to Cell Fate Specification.

Sensory organs are essential for animals to receive and sense the environment. Drosophila external sensory (ES) organs provide a genetically advantageous system to study various aspects of sensory organ development, such as patterning and cell fate specification. Each ES organ is derived from a single sensory organ precursor (SOP), which is specified by the bHLH-type proneural proteins Achaete (Ac) and Scute (Sc). SOP then divides asymmetrically to generate two secondary precursors pIIa and pIIb, which divide again to give rise to all four daughter cells that constitute an ES organ. In this grant, we propose to study functions of two important cellular components, the COP 9 signalsomone (CSN) and nuclear actin, in ES organ development. In the first part of proposal, we propose to analyze the role of CSN. Two interesting phenotypes were observed in CSN mutants: (1) pIIb cells are transformed into pIIa cells, leading to ES organs with two hairs and one fused socket. (2) non-innervated bristles at the posterior wing margin (PWM) are transformed into neuron-innervated ES organs, indicating a novel role of CSN in sensory organ patterning. In this proposal, we would like to study how CNS regulates the numb-Notch-phyl-ttk pathway to mediate pIIa/pIIb fate specification, and how CSN might repress senseless (sens) expression to specify PWM non-innervated bristles. We will also examine the functional interaction between CSN and the apoptotic pathway, and between CSN and the ecdysone pathway. Proneural proteins play pivotal roles in neurogenesis in both invertebrates and vertebrates. Through biochemical approach, we identified nuclear actin as the interacting partner of the Ac-Daughterless (Da) heterodimeric complex. In addition to its traditional role in cytoskeleton, actin is shown to play important roles in nuclear events such as mRNA processing and transcription. Reporter assay in S2 cells and genetic analysis support the role of actin in the ac- and sc-mediated transcriptional activation and ES organ formation. In the second part of this proposal, we will further dissect the interaction between nuclear actin and the Ac-Da proneural complex, and study the molecular functions of polymeric actin in proneural protein-dependent transcription. Finally, we would like to identify and study the interactome of Ac and Sc in the specification and differentiation of Drosophila neural precursors.

Project ID:PA10007-0216
External Project ID:NSC100-2311-B182-002