Control of perineurial glial growth in Drosophila melanogaster

Although intercellular communication within peripheral nerves is critical to the structure and function of the nervous system, it is incompletely understood. Drosophila peripheral nerves comprise motor and sensory axons bundled by peripheral glia (Schwann cells) and wrapped by perineurial glia (perineurium). I have shown that growth of the perineurial glia is controlled by signaling pathways involving six genes: push, which encodes a large Zn2+ finger containing protein; amn which encodes a putative neuropeptide; Axs, which is suggested to encode a G-protein coupled receptor; ine, which encodes a putative neurotransmitter/osmolyte transporter; eag, which encodes a potassium channel; and NF1, which encodes neurofibromin and is the Drosophila ortholog of the human gene responsible for Neurofibromatosis type1. I provide evidence that neurofibromin, in accordance with its role as a Ras guanosine triphosphatase activating protein (Ras GAP), acts to down regulate Ras activity to control perineurial glial growth. My work suggests that loss of neurofibromin leads to an increase in Ras activity in the peripheral glia that, in conjunction with loss of either Ine or Push, introduces a cell-nonautonomous signal that promotes growth of the perineurial glia. I have also found that Push does not act through Ras to control perineurial glial growth. My working hypothesis is that Amn acts through two separate pathways, one involving Push and the other involving neurofibromin, to inhibit perineurial glial growth. In this model, a separate pathway involving the substrate neurotransmitter of Ine promotes perineurial glial growth. I speculate that Ine may act to remove its substrate neurotransmitter from the extracellular space, thereby inhibiting the neurotransmitter from acting through its receptor to promote perineurial glial growth. Alternatively, Ine may control perineurial glial growth via its role as an osmolyte transporter. Eag may act to inhibit perineurial glial growth by repressing release of factors from the neurons or peripheral glia through maintaining these cells in a hyperpolarized state.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Natural Sciences

Grantor

Rice University

Year dc:date.issued

2003

Author dc:creator

• Yager, James Christopher

Advisor dc:contributor.advisor

• Stern, Michael

• Neurosciences
• Genetics

Statement dc:rights

• Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1911/18585

OAI identifier oai:identifier

oai:repository.rice.edu:1911/18585