Molecular Mechanisms Underlying Stress-Induced Glia Remodeling in the Nematode C. Elegans

<p>Animals can adapt to long-term environmental changes by modifying their behavior, which can be accompanied by structural alterations of the nervous system. Such alterations are common in sensory organs, composed of sensory neurons and glia, which initially detect environmental stress. The molecular mechanisms driving cell shape remodeling following environmental stress and the effects of such remodeling on animal survival are not well understood. C. elegans is an excellent model in which to study neuronal and glial cell remodeling. Under normal growth conditions, the sensory receptive endings of the bilateral AWC sensory neurons, which respond to volatile odorants, are individually ensheathed by processes of adjacent amphid sheath (AMsh) glial cells. Upon exposure to high temperature, starvation, or crowding, animals enter an alternative developmental state, called dauer, in which bilateral AMsh glia membranes surrounding the AWC neuron fuse, connecting the two glial cells, and allowing the AWC neuronal receptive endings to expand. Previous studies from our lab identified several AMsh glia proteins required for remodeling. These include (1) the cell fusion protein AFF-1, (2) a VEGFR-related protein VER-1, (3) the Otd/Otx transcription factor TTX-1, and (4) the zinc-finger transcription factor ZTF-16. ver-1 expression in AMsh glia is induced by dauer entry or by cultivation at high temperature, and requires direct binding of TTX-1 to ver-1 regulatory sequences. To identify additional genes involved in stress-induced sensory organ remodeling, we performed a forward genetic screen, seeking mutants in which ver-1 expression at high temperature is not induced. One mutant recovered from this screen harbors a causal lesion in F47D2.11 gene, which encodes a 7- transmembrane G-protein coupled receptor (GPCR). Mutations in F47D2.11 not only block ver-1 induction, but also prevent dauer-induced AMsh glia remodeling and result in a delay in exit from the dauer state following exposure to a favorable environment. F47D2.11 mutants can be rescued by expression of the wild-type cDNA in AMsh glia but not in AWC neurons. These results implicate F47D2.11 in the sensation of dauer conditions in AMsh glia, required for dauer-induced glial remodeling and timely dauer exit.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2019

Author dc:creator

• Lee, In Hae

Contributors dc:contributor

• Shai Shaham

• C. elegans
• AMsh glia
• sensory remodeling
• dauer
• GPCR F47D2.11
• ver-1 expression
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/510

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1515