Nejire, a CBP/p300 Family Transcription Factor, Regulates Dendritic Development by Modulating the Localization of the Krüppel-like Transcription Factor Dar1 in Drosophila Sensory Neurons




Rubaharan, Myurajan

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Dendrite morphogenesis represents a critical process in the establishment, maintenance and modulation of neural connectivity that is the basis of a functional nervous system. Dendrites, as the primary sites of synaptic and/or sensory input largely determine the size and nature of the neuronal receptive field. The Drosophila melanogaster peripheral nervous system (PNS) has emerged as an excellent model system for studying molecular mechanisms underlying class specific dendrite development. Dendritic arborization (da) neurons are grouped into four distinct classes (I- IV) based upon increasing orders of dendritic complexity (Grueber et al., 2002). A recent study has identified dar1, a Krüppel-like transcription factor, as an essential regulator involved in controlling dendrite development and growth via microtubule modulation (Ye et al., 2011). Interestingly, at the embryonic stage Dar1 protein exhibits nuclear localization in all da neuron subclasses, however at the third instar larval stage of development, Dar1 exhibits a subcellular shift towards class-specific differential localization. Specifically, Dar1 is primarily nuclear in the morphologically simple class I neurons, in contrast to largely cytoplasmic localization in the highly complex class IV da neurons. This observation led us to investigate putative protein interaction partners of Dar1 that potentially regulate this class specific differential localization, and the result of perturbing this localization. We conducted a pilot RNAi screen of putative Dar1- interacting proteins to investigate their potential mechanistic role(s) in dendrite development and Dar1 differential localization in class IV da neurons. From this pilot screen, we identified the CBP/p300 homolog nejire (nej) as a novel regulator of dendritic development that also modulates Dar1 subcellular localization. We have conducted detailed structure-function studies using domain-specific deletions of nej that have provided further insights into the specific role of different protein domains in mediating distinct aspects of dendritic growth. Furthermore, we have used these domain-specific deletion constructs to elucidate the interaction between Dar1 and Nej. 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.



Dendrites, Neuron, Drosophila, Transcription factor, Nejire, Dar1