L'Etoile, Noelle, Cha, Amanda, Ghafari, Ghazal, Llamas, Sara, Young, Jared, Janzen, Laine, Stinson, Pilar, Summers, Stephanie
[
International Worm Meeting,
2011]
Context cues play a role in compulsive and addictive behaviors by endowing accompanying stimuli with increased salience. For example, olfactory cues such as food odors accompany the reinforcing stimulus of the food itself, and thus stimulate cravings for the reinforcing stimulus. We suggest important modulation of odor processing may occur in olfactory sensory neurons, and indeed recent studies have indicated that responses to odors may be modified early in the olfactory pathway (1,2). Olfactory adaptation is a basic form of learning that causes desensitization of an organism to an odorant after a prolonged period of exposure. Studies have shown that adaptation to an odorant can be repressed by the presence of food in the model organism C.elegans (3,4). This block of adaptation involves inhibition of changes in the primary sensory neuron which are associated with olfactory adaptation. As part of a larger project to study the molecular, cell biological, and circuit level mechanisms by which food-derived signals affect odor signaling and long-term plasticity in the model organism C.elegans, this project will attempt to identify new genes involved in the inhibition of long-term neuronal plasticity by food signaling in the sensory neuron (AWC). To identify new genes involved in the food block on adaptation, we are using an unbiased forward genetic screen to isolate mutants. This foundational project will contribute to a larger endeavor to reveal how rewarding stimuli alter signal processing within the primary sensory neuron and may inspire therapies for controlling debilitating compulsive behaviors, such as over eating or drug addiction. 1. Li W, Howard JD, Parrish TB, Gottfried JA. Aversive learning enhances perceptual and cortical discrimination of indiscriminable odor cues. Science. 2008 Mar 28;319(5871):1842-5. 2. Doucette W, Gire DH, Whitesell J, Carmean V, Lucero MT, Restrepo D. Associative Cortex Features in the First Olfactory Brain Relay Station, Neuron. 2011 Mar;69(6):1176-1187. 3. L'Etoile ND, Coburn CM, Eastham J, Kistler A, Gallegos G, Bargmann CI. The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron. 2002 Dec 19;36(6):1079-89. 4. Colbert HA, Bargmann CI. Environmental signals modulate olfactory acuity, discrimination, and memory in Caenorhabditis elegans. Learn Mem. 1997 Jul-Aug;4(2):179-91.
[
European Worm Meeting,
2006]
Sara Vassalli and Alex Hajnal. During vulval development in the hermaphrodite, three out of six equivalent vulval precursor cells (the VPCs P3.p to P8.p) are induced by a signal from the gonadal anchor cell (AC). The LIN-3 EGF growth factor produced by the AC activates the EGFR/RAS/MAPK pathway in the VPCs to specify the primary cell fate. Prior to vulval induction, the gonad is separated from the VPCs by two basal laminas covering each tissue such that the position of the AC relative to the VPCs is variable when the animal moves. At the time of vulval induction in the early L3 stage, however, the AC attaches to the basal side of the future primary cell P6.p. After the first round of vulval cell divisions (Pn.px stage), the basal laminas separating the gonad from the vulval cells start to dissolve precisely under the AC. After the second round of divisions (Pn.pxx stage), the basal laminas between the AC and the four primary vulval cells are interrupted, and the AC invades the vulval tissue.. While the mechanism of vulval induction is well studied, less is known about genes regulating the attachment of the AC to P6.p and the following invasion step. To study these two processes, we performed a forward genetic screen for mutants with defects in AC positioning and/or invasion. Since worms with an abnormal or missing connection between the gonad and the vulva usually display a protruding vulva (Pvl) phenotype, we first screened for animals with a Pvl phenotype and then examined them for defects in the positioning or invasion of the AC. Among 5300 F1 clones, we identified 8 sterile mutants with a misplaced AC and 2 mutants, in which the AC is normally positioned but fails to dissolve the basal laminas and invade the vulval tissue. Details about the cloning and analysis of the genes identified in this screen will be presented at the meeting.