Nejire, a CBP/p300 family transcription factor, regulates dendritic development by modulating the localization of the Krüppel-like transcription factor Dar1 in Drosophila da neurons. Myurajan Rubaharan, Srividya C Iyer, Eswar P R Iyer, Daniel N Cox. School of Systems Biol., Krasnow Inst. Adv. Study, George Mason University, Fairfax, VA.

   The Drosophila PNS has emerged as an excellent model system for studying molecular mechanisms underlying class specific dendrite development. Dar1, a Krüppel-like transcription factor, has been previously identified as an essential regulator of dendrite development via microtubule modulation. Interestingly, while Dar1 is equivalently expressed in all da neurons at the embryonic stage, Dar1 exhibits differential localization in da neuron subclasses at the larval stage. Dar1 is primarily nuclear in the morphologically simple class I neurons as opposed to the largely cytoplasmic localization observed in the complex class IV da neurons. Here we provide novel insights on the mechanism of differential localization of Dar1 protein, and its corresponding effects on dendrite development. Via an RNAi-based approach, we screened the predicted Dar-1 protein-interaction partners for the ability to regulate Dar1 localization as well as the effects of perturbing its differential localization on dendrite development. Through this approach, we have identified nejire as a novel regulator of dendritogenesis that acts in modulating Dar1 localization. Nejire is expressed in a differential pattern among da neurons of varying complexity that is consistent with the larval Dar1 expression pattern. Moreover, we have conducted detailed structure-function studies using domain specific deletions of nejire that have provided further insights into the specific role of different protein domains in mediating distinct aspects of dendritic growth. Finally, we have investigated the regulatory role of Prospero in modulating expression levels of Nejire to affect dendrite morphology. Collectively, these analyses contribute to our understanding of molecular mechanisms of combinatorial transcription factor activity at a class-specific level and how this regulation contributes to specification of distinct neuronal morphologies that underlie the establishment of complex neural networks.