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Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Biological Sciences
First Advisor
Joy Alcedo
Abstract
The C. elegans insulin-like peptide (ILP) network provides a means to coordinate the multiple outputs of the insulin signaling pathway, which are responses to the diverse environmental inputs that an animal receives throughout its life. This coordination is vital for the animal to thrive and is exemplified by the network’s integration of the combinatorial activities of the different ILPs that regulate the animal’s developmental plasticity. Thus, the developmental switches between growth under favorable environments and dauer arrest under harsh environments highlight the importance of the ILP network function for survival.
How then is this network regulated, where one ILP affects the expression of another ILP? This network is distributed across multiple neurons that can communicate through synapses, thereby making synaptic proteins candidate regulators of the network. Here I identify a component of electrical synapses, the gap junction protein CHE-7, to regulate the expression of a major node of this network, the ILP ins-6, as the animal switches between developmental programs. During the dauer entry decision stage, when the animal is weighing its decision to enter dauer or to stay in the growth program, CHE-7 modulates the ASJ sensory neuron expression of ins-6, where CHE-7 favors growth. Once in dauers, CHE-7 facilitates the rise in ins-6 expression, again in ASJ, as the animal prepares to exit into the growth program when the environment improves. Thus, I show that CHE-7, which also acts from the neuron ASJ, ensures reproductive growth through the activities of INS-6 and at least one other ILP of the network, DAF-28.
Gap junctions allow the flow of small molecules between two cytosols, which can be ions, secondary messengers, or metabolites, among others. The involvement of a gap junction protein in promoting developmental plasticity signifies the need for a rapid mechanism for intercellular communication that allows the animal to switch quickly between two programs in response to the changing quality of its environment. Thus, CHE-7 and potentially other gap junction proteins should promote the rapid integration of the different ILP activities within the network to coordinate their multiple outputs for increased survival of the animal.
Insulin signaling is conserved from C. elegans to humans. Gap junctions are also ubiquitous and important across the animal kingdom. Accordingly, it is very possible that gap junctions will also modulate neural insulin signaling in other animals, including humans, where gap junction dysfunction can underlie aberrant insulin pathway activities and multiple disease states.
Recommended Citation
Pereira, Bianca Priya, "Gap Junction Protein Che-7 Modulates The Insulin-Like Peptide Network From Sensory Neurons To Promote Developmental Plasticity" (2025). Wayne State University Dissertations. 4265.
https://digitalcommons.wayne.edu/oa_dissertations/4265