The territories of dendritic and axonal arbors determine how neurons receive and transmit information in the nervous system, and disruptions of dendritic and axonal morphology are associated with numerous neurological disorders. Many types of dendrites and axons are organized according to the principles of tiling and self-avoidance, in which arbors of neurons expand until they abut neighboring arbors. Both self-avoidance and tiling ensure that sensory or synaptic inputs in the nervous system are sampled completely and non-redundantly, a critical requirement for functional neuronal circuits, however we still know little about how such territories are built. We propose to examine the mechanism of dendritic tiling in the Drosophila sensory system, a powerful model for studies of the molecular control of neuronal morphogenesis. We propose to examine the molecular basis for dendrite-dendrite interactions and dendrite-substrate interactions that control tiling behavior of dendrites To accomplish our aims we will perform laser cell ablations to eliminate neurons and their dendrites to determine whether dendrite-dendrite interactions are important for field formation. We will use gene knock out approaches to eliminate the function of genes and assess necessity for tiling, and, conversely, misexpress genes to determine whether they are sufficient to promote tiling. We will study the re-use of signals that are important for dendritic tiling during axon tilng to explore whether dendrites and axons are patterned by similar cellular and molecular mechanisms. We expect that these results will be highly relevant for understanding the mechanisms by which proper dendritic and axonal patterning is achieved in the nervous system, and how alteration or disruption of molecular programs might underlie developmental defects.
Proper patterning of neuronal arbors is critical for normal development and function of the nervous system. We aim to study how cell-cell recognition controls the arborization patterns of axons and dendrites in the nervous system. Aberrant neuronal dendrite morphology is associated with numerous neurological disorders, making study of the signaling molecules that pattern dendrites and axons important for understanding the basis for human health and disease.
|Singhania, Aditi; Grueber, Wesley B (2014) Development of the embryonic and larval peripheral nervous system of Drosophila. Wiley Interdiscip Rev Dev Biol 3:193-210|
|Kim, Michelle E; Shrestha, Brikha R; Blazeski, Richard et al. (2012) Integrins establish dendrite-substrate relationships that promote dendritic self-avoidance and patterning in drosophila sensory neurons. Neuron 73:79-91|
|Shrestha, Brikha R; Grueber, Wesley B (2011) Analysis of dendrite development in Drosophila embryos. Cold Spring Harb Protoc 2011:967-72|
|Matthews, Benjamin J; Grueber, Wesley B (2011) Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites in Drosophila. Curr Biol 21:1480-7|
|Shrestha, Brikha R; Grueber, Wesley B (2011) Methods for exploring the genetic control of sensory neuron dendrite morphogenesis in Drosophila. Cold Spring Harb Protoc 2011:910-6|
|Shrestha, Brikha R; Grueber, Wesley B (2011) Generation and staining of MARCM clones in Drosophila. Cold Spring Harb Protoc 2011:973-9|
|Grueber, Wesley B; Sagasti, Alvaro (2010) Self-avoidance and tiling: Mechanisms of dendrite and axon spacing. Cold Spring Harb Perspect Biol 2:a001750|