MARC Record from marc_columbia

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001 12848023
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008 170913s2013 nyu|||| om 00| ||eng d
035 $a(OCoLC)1004791194
035 $a(OCoLC)on1004791194
035 $a(NNC)ACfeed:legacy_id:ac:183398
035 $a(NNC)ACfeed:doi:10.7916/D8MG7WQ8
035 $a(NNC)12848023
040 $aNNC$beng$erda$cNNC
100 1 $aSmith, Heidi.
245 10 $aUnderstanding Chemotaxis in the Nematode Caenorhabditis elegans :$bFrom Molecules to Behavior /$cHeidi Smith.
264 1 $a[New York, N.Y.?] :$b[publisher not identified],$c2013.
300 $a1 online resource.
336 $atext$btxt$2rdacontent
337 $acomputer$bc$2rdamedia
338 $aonline resource$bcr$2rdacarrier
502 $aThesis (Ph.D.)--Columbia University, 2013.
500 $aDepartment: Biological Sciences.
500 $aThesis advisor: Hobert Oliver.
520 $aHow animal behavior is controlled at the molecular and cellular levels is still largely mysterious. Here, I document my studies on the mechanisms controlling a simple behavior--chemotaxis--in the nematode worm Caenorhabditis elegans. My work focuses on a pair of amphid sensory neurons at the head end of the worm called ASEs. The neurons are exposed and respond to environmental chemical signals, and instruct downstream locomotory responses that cause the worm to move up or down chemical gradients. The ASE neurons are morphology similar and arranged symmetrically across the head. Yet, it has been known for some time that they show differences in which ionic signals they are primarily responsive to (Na+/, Cl/, K+) in regards to chemotaxis behavior. Furthermore, it had been observed that the ASEs also express distinct sets of genes, in particular, receptor-type guanylyl cyclases (rGCs). This thesis begins with my contribution to a study of the function of ASE asymmetry in chemotaxis. I, along with another graduate student, found that an additional four salt ions (Br-, Li+/, I /, Mg2+) are sensed by either ASER (right) or ASEL (left) neurons.
520 $aEvidence is presented that this laterality in ion receptivity allows the nematode to discriminate right-sensed salt cues in the background of left-sensed cues and vice versa. We further investigated what role asymmetrically expressed rGCs might play in the regulation of chemotaxis. Using mutants for some of these genes, we found that, depending on the rGC, they confer chemotactic responsiveness to one, two, or several salts. Hence, asymmetry in ASE ion sensitivity is conferred, at least in part, by asymmetry in rGC expression. Next, I attempted to test whether rGCs act as direct salt receptors, or function further downstream to modulate signal transduction. To address this question, I used chimeras made with three different ASER-expressed rGCs, all of which have the same basic domain architecture. I performed domain-swap experiments where the extracellular domain of one rGC was exchanged with the intracellular domain of another in all possible combinations. I was able to show that the extracellular domain is the region that confers specificity to which ions these rGCs respond.
520 $aFurthermore I carried out experiments to test the idea that rGCs act as heterodimers, by heterologously expressing two rGCs together in all amphids other than ASEs. By doing this, I was able to confer a new ion-sensitivity function to the cells; like ASE neurons, they could sense ions and elicit a chemotactic response. Together these independent lines of evidence suggest that rGCs permit amphids to sense certain salts, and may therefore be acting as salt receptors. Finally, in an investigation of some chemotaxis mutants which employed whole genome sequencing, a particularly interesting mutant was uncovered that encodes a previously undescribed cyclic nucleotide-gated channel (CNG), che-6. I characterize the potential role of che-6, and propose that it encodes a novel CNG that functions in salt chemotaxis behavior and most likely acts downstream of rGCs. Taken together, these data shed light on the mechanism of salt chemotaxis in nematodes, and provide an example of how genes govern basic behaviors in this relatively simplified animal.
520 $aI discuss what remains to be understood in this system, and how it compares to chemosensory systems in other animal species. The results are also interpreted in the light of maximizing the sophistication of a nervous system that is cell number- and size-limited.
653 0 $aGenetics
653 0 $aNeurosciences
653 0 $aPsychology
856 40 $uhttps://doi.org/10.7916/D8MG7WQ8$zClick for full text
852 8 $blweb$hDISSERTATIONS