PgmNr W4103: Scaffolding Cells and Associated Molecular Factors in C. elegans Nerve Ring Development.

Authors:
Kris Barnes; Pavak Shah; Li Fan; Anthony Santella; Nhan Nguyen-Tran; Zhirong Bao


Institutes
Memorial Sloan Kettering, New York, NY.


Keyword: Tissue organization/organogenesis

Abstract:

The embryonic development of the C. elegans nerve ring has remained an open and largely unexplored problem since John White mapped the nervous system in 1986.  Genetic mutants with abnormal post embryonic nerve ring morphologies exist, but the specific cellular events in the developmental process and the function of associated molecular factors have not been well characterized.  This is in part due to the difficulties involved with combining high resolution imaging with already time consuming forward genetic screens.  We hypothesize a scenario where specific cells act as a scaffold to draw in surrounding axons and promote outgrowth along a concise and consistent path.  This process must involve at least 3 main components: the development of the scaffold itself, local paracrine signaling which causes spatially separated axons to be drawn in to the scaffold, and a stage where cell specific juxtacrine factors promote the outgrowth of axons along specific paths.  Initial anatomical observations point to several possible areas of interest which lie adjacent to the proto nerve ring including the GLR’s, the pharyngeal primordium cells, and surrounding rows of neuroblasts which also lie parallel yet lateral to the incoming axon fibres.  We aim to establish a functional relationship at the level of causation to determine which of these areas are involved in the scaffold. Furthermore, multiple incoming axon bundles are being studied for their spatial and temporal relation, and juxtacrine factors of interest are being identified with localized expression.  We are finding specific genetic and anatomical perturbations leading to impairment of these processes, including results from mutant analysis and automated cell specific ablation experiments.