Genetic Analysis of Bacterial Food Perception and its Influence on Foraging Behavior in C. elegans

Abstract

The ability to adapt to changes in food conditions is critical for organismal homeostasis and survival. In this thesis, I explore the genetic and neuroendocrine mechanisms by which C. elegans evaluates bacterial food conditions and accordingly alters development and behavior. In Chapter One, I discuss the relationship between C. elegans and its bacterial diet. The influence of food on behavior suggests the presence of a gut-“brain” axis that senses and communicates information about nutritional state to the nervous system to elicit a behavioral response.

In Chapter Two, I characterize a gain-of-function allele of scd-2, the C. elegans Anaplastic Lymphoma Kinase (ALK) gene ortholog, scd-2(syb2455),which I designed based on an oncogenic mutation in ALK. While animals with loss-of-function mutations in scd-2 are dauer-formation defective, scd-2(syb2455) animals enter dauer regardless of food conditions. In Chapter Three, I report that SCD-2 also regulates the food-dependent feeding and foraging behaviors known as dwelling and roaming; scd-2(syb2455) animals roam more and scd-2 loss-of-function animals roam less than wild type. Additionally, in contrast to wild-type animals, which express the gene encoding the TGF- signaling ligand DAF-7 exclusively in the ASI chemosensory neurons, scd-2(syb2455) animals constitutively express daf-7 in both the ASI and ASJ neurons. The expression of daf-7 in the ASJ neurons drives roaming in these animals. I demonstrate that daf-7 expression in the ASJ neurons is also affected by food; ingested food in the pharynx inhibits daf-7 expression in the ASJ neurons through SCD-2 signaling. From these data we propose a positive-feedback loop that regulates roaming behavior: in the absence of ingested food, active SCD-2 induces daf-7 expression in the ASJ neurons to promote roaming, which further reduces food consumption. To further investigate how daf-7 neuroendocrine signaling responds to nutritional state, in Chapter Four I describe a screen for satiety signals using the nutritional state-dependent daf-7 expression in the ASJ neurons in males as a readout for communication along the gut-“brain” axis. This screen yielded a loss-of-function allele of che-3 and a gain-of-function allele of pdfr-1. In Chapter Five, I discuss future directions for investigating how C. elegans interacts with its food environment.