|Ph.D Student||Oren Meital|
|Subject||Mechanisms of Neuronal Branching|
|Department||Department of Biology||Supervisor||Professor Benjamin Podbilewicz|
|Full Thesis text|
The mechanisms controlling the formation and maintenance of neuronal trees are poorly understood. I examined the dynamic development of two arborized mechanoreceptor neurons (PVDs) required for reception of strong mechanical stimuli in Caenorhabditis elegans. The PVDs elaborated dendritic trees comprising structural units I call “menorahs”. I studied how the number, structure and function of menorahs were maintained. I found a novel role for eff-1 (epithelial fusion failure) in dendrite arborization. EFF-1 is the founder member of a family of membrane proteins that are essential and sufficient to fuse cells. Unexpectedly, eff-1 mutants displayed hyperbranched disorganized menorahs. When expressed in the PVDs, EFF-1 was sufficient to reduce the number of branches and to rescue disorganized menorahs. Live confocal imaging revealed that EFF-1 controls the balance between the number, structure and function of menorahs mainly by stimulating the retraction of defective outgrowth, but also by fusing abnormal branches and forming loops that restrict further growth. Thus EFF-1 activities may act as a quality control mechanism during the sculpting of dendritic trees.
Dendritic arborization of nociceptors is a process essential for sensing pain and stimuli that can cause damage to the organism. To determine whether dendritic arborization is affected by injury, I severed dendrites by laser nanosurgery and followed their fate. I found that broken dendrites regenerated via fusion of newly sprouted branches that grew over the injury site and fused to one another. In addition, menorah-menorah fusion prevented degeneration independently of the reconnection of the severed branches. Finally, excess branches produced during regeneration were pruned leading to the formation of simplified dendritic arbors, which resembled the initial pattern. Very little is known about the genetic pathway of regeneration and degeneration triggered by experimental dendrotomy. I showed that the nuclear hormone receptor nhr-25 is required to eliminate excess dendrites, sculpt right-angle menorahs and prevent menorah-menorah fusion during development. Dendrotomized nhr-25 mutant animals, failed to trim excess dendrites that continued to grow for days after injury. My results demonstrate that nhr-25 is essential for normal arborization and for pruning after dendrotomy in C. elegans. This research is the first step in the molecular genetic analysis of PVD arborization in C. elegans and provides the tool kit to unravel the mechanisms underlying dendrite development.