PgmNr D1249: The conserved microtubule-associated protein Mini Spindles regulates dendrite branching and self-avoidance in Drosophila class IV dendritic arborization neurons.

Authors:
Mala Misra 1 ; Noor Anvery 1 ; Claire Kittock 1 ; Hendia Edmund 2 ; Elizabeth Gavis 2


Institutes
1) Colgate University, Hamilton, NY; 2) Princeton University, Princeton, NJ.


Keyword: dendrites

Abstract:

Neuronal dysgenesis is a common feature of diverse neuropsychiatric and neurodevelopmental disorders, underscoring the need for a more comprehensive understanding of the molecular mechanisms underlying neuronal morphogenesis. The dendrites of Drosophila larval class IV dendritic arborization (c4da) neurons provide an excellent model system to study the regulation of dendrite morphogenesis because their complex branching patterns show clear parallels to those seen in vertebrates, and their two-dimensional organization on the surface of the larva allows for easy visualization. We capitalized on these properties in designing a two-tiered genetic screen to identify genes that (1) encode dendrite-localized mRNAs, and (2) regulate dendrite morphogenesis. The goal of the screen was to connect the local regulation of protein synthesis with dynamic morphogenetic events in the dendrites. One positive candidate arising from this effort was the gene mini spindles (msps), which encodes a microtubule associated protein homologous to XMAP215-family proteins in vertebrates. Previous studies have demonstrated that Msps regulates microtubule nucleation and promotes dynamic instability. We therefore hypothesized that it might play a role in regulating cytoskeletal events important for the growth and/or retraction of dendrite branches in c4da neurons. RNAi-mediated knockdown of msps expression in c4da neurons resulted in a modest but significant loss of branching, supporting this initial hypothesis. Strikingly, mspsRNAi dendrites also exhibited more than twice as many self-crossings within the receptive field as control yw dendrites.  Some previously characterized instances of aberrant c4da self-crossing have been linked to the enclosure of dendrites by overlying epidermal cells and a consequent loss of the characteristic two-dimensional array; immunostaining for Coracle, a marker of enclosure, confirmed that self-crossing dendrites in mspsRNAi neurons also exhibit this behavior. The localization of msps mRNA to dendrites and the disorganization of dendrite branching in the absence of Msps protein suggest a preliminary model in which local control of Msps expression could regulate cytoskeletal dynamics and dendrite morphogenesis in response to local signaling between the neuron and the external environment.



Flybase Genetic Index:
1. FlyBase gene symbol: msps; FBgn: FBgn0027948