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Comments on Liberatore, K. et al. (2019) International Worm Meeting "FAX-1 Interneurons and Insulin Signaling Regulate Arousal and Quiescence." (0)
Overview
Liberatore, K., He, Z., Koitz, F., Silver, D., & Wightman, B. (2019). FAX-1 Interneurons and Insulin Signaling Regulate Arousal and Quiescence presented in International Worm Meeting. Unpublished information; cite only with author permission.
fax-1 encodes a nuclear receptor that is the ortholog of PNR in mammals and functions in specifying neuronal identity during development. fax-1 is expressed in a limited number of interneurons, including AVA, AVE, and AVK. The daf-2 insulin receptor is the key mediator of insulin signaling in which downstream activation of daf-16/FOXO-like transcription factor is implicated in increased longevity and dauer arrest. Arrest assays of daf-2(e1370); fax-1 double mutants reveal quiescent arrest at hatching. This novel peri-hatching arrest phenotype is analogous to sleep, as it can be reversed with flashes of aversive blue light. These animals are rescued by downstream mutations in daf-16 and daf-18/PTEN, but not components of the TGF-? pathway, confirming that insulin and neuronal signaling control quiescent arrest. Interneuron AVK contributes to arousal and expresses fax-1, which makes it a candidate as a key mediator of peri-hatching arrest. If we selectively express fax-1 in a subset of neurons in daf-2(e1370); fax-1 double mutants, we can determine in which interneurons fax-1 expression is responsible for peri-hatching arrest. We are performing cell specific rescue assays with transgenic double mutant animals with extrachromosomal arrays that drive FAX-1 expression under the control of neuron-specific promoters. glr-2, npr-1, glr-5:: fax-1::gfp fusions reveal that broad expression of FAX-1 in AVA, AVE, AVK, SIB, and RIC interneurons rescues double mutant animals from quiescence. However, animals are not rescued when FAX-1 is selectively expressed in AVA and AVE. These data suggest that AVK may be a key interneuron mediator that regulates quiescence at hatching.
Affiliation:
- Muhlenberg College, Allentown, PA