scholarly journals Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons of Caenorhabditis elegans

2018 ◽  
Author(s):  
Chaogu Zheng ◽  
Felix Qiaochu Jin ◽  
Brian Loeber Trippe ◽  
Ji Wu ◽  
Martin Chalfie

AbstractTerminal differentiation generates the specialized features and functions that allow postmitotic cells to acquire their distinguishing characteristics. This process is thought to be controlled by transcription factors called “terminal selectors” that directly activate a set of downstream effector genes. In Caenorhabditis elegans the differentiation of both the mechanosensory touch receptor neurons (TRNs) and the multidendritic nociceptor FLP neurons utilize the terminal selectors UNC-86 and MEC-3. The FLP neurons fail to activate TRN genes, however, because a complex of two transcriptional repressors (EGL-44/EGL-46) prevents their expression. Here we show that the ZEB family transcriptional factor ZAG-1 promotes TRN differentiation not by activating TRN genes but by preventing the expression of EGL-44/EGL-46. Since EGL-44/EGL-46 also inhibits the production of ZAG-1, these proteins form a bistable, negative feedback loop that regulates the choice between the two neuronal fates.Summary statement:Transcriptional repressors regulate binary fate choices through reciprocal inhibition during terminal neuronal differentiation. Specifically, ZEB family transcription factor safeguards fate specification of touch receptor neuron by inhibiting TEA domain-containing repressor.

Development ◽  
2018 ◽  
Vol 145 (22) ◽  
pp. dev168096 ◽  
Author(s):  
Chaogu Zheng ◽  
Felix Qiaochu Jin ◽  
Brian Loeber Trippe ◽  
Ji Wu ◽  
Martin Chalfie

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 773-783 ◽  
Author(s):  
S. Mitani ◽  
H. Du ◽  
D.H. Hall ◽  
M. Driscoll ◽  
M. Chalfie

Six touch receptor neurons with distinctive morphological features sense gentle touch in Caenorhabditis elegans. Previous studies have identified three genes (lin-32, unc-86 and mec-3) that regulate touch cell development. However, since other cell types also require these genes, we suspected that other genes help restrict the expression of touch cell characteristics to the six neurons seen in the wild type. To identify such genes, we have examined mutants defective in genes required for the development of other C. elegans cells for changes in the pattern of touch cell-specific features. Mutations in seven genes either reduce (lin-14) or increase (lin-4, egl-44, egl-46, sem-4, ced-3 and ced-4) the number of touch receptor-like cells. The combinatorial action of these genes, all of which are required for the production of many cell types, restrict the number of cells expressing touch receptor characteristics in wild-type animals by acting as positive and negative regulators and by removing cells by programmed cell death.


2015 ◽  
Vol 5 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Xiaoyin Chen ◽  
Margarete Diaz Cuadros ◽  
Martin Chalfie

Abstract Caenorhabditis elegans senses gentle touch along the body via six touch receptor neurons. Although genetic screens and microarray analyses have identified several genes needed for touch sensitivity, these methods miss pleiotropic genes that are essential for the viability, movement, or fertility of the animals. We used neuronally enhanced feeding RNA interference to screen genes that cause lethality or paralysis when mutated, and we identified 61 such genes affecting touch sensitivity, including five positive controls. We confirmed 18 genes by using available alleles, and further studied one of them, tag-170, now renamed txdc-9. txdc-9 preferentially affects anterior touch response but is needed for tubulin acetylation and microtubule formation in both the anterior and posterior touch receptor neurons. Our results indicate that neuronally enhanced feeding RNA interference screens complement traditional mutageneses by identifying additional nonviable genes needed for specific neuronal functions.


2015 ◽  
Vol 112 (37) ◽  
pp. 11690-11695 ◽  
Author(s):  
Yushu Chen ◽  
Shashank Bharill ◽  
Ehud Y. Isacoff ◽  
Martin Chalfie

Caenorhabditis elegans senses gentle touch in the six touch receptor neurons (TRNs) using a mechanotransduction complex that contains the pore-forming degenerin/epithelial sodium channel (DEG/ENaC) proteins MEC-4 and MEC-10. Past work has suggested these proteins interact with the paraoxonase-like MEC-6 and the cholesterol-binding stomatin-like MEC-2 proteins. Using single molecule optical imaging in Xenopus oocytes, we found that MEC-4 forms homotrimers and MEC-4 and MEC-10 form 4:4:10 heterotrimers. MEC-6 and MEC-2 do not associate tightly with these trimers and do not influence trimer stoichiometry, indicating that they are not part of the core channel transduction complex. Consistent with the in vitro data, MEC-10, but not MEC-6, formed puncta in TRN neurites that colocalize with MEC-4 when MEC-4 is overexpressed in the TRNs.


2011 ◽  
Vol 31 (35) ◽  
pp. 12695-12704 ◽  
Author(s):  
J. Arnadottir ◽  
R. O'Hagan ◽  
Y. Chen ◽  
M. B. Goodman ◽  
M. Chalfie

2017 ◽  
Author(s):  
Patrick D. McClanahan ◽  
Joyce H. Xu ◽  
Christopher Fang-Yen

AbstractThe roundworm Caenorhabditis elegans is an important model system for understanding the genetics and physiology of touch. Classical assays for C. elegans touch, which involve manually touching the animal with a probe and observing its response, are limited by their low throughput and qualitative nature. We developed a microfluidic device in which several dozen animals are subject to spatially localized mechanical stimuli with variable amplitude. The device contains 64 sinusoidal channels through which worms crawl, and hydraulic valves that deliver touch stimuli to the worms. We used this assay to characterize the behavioral responses to gentle touch stimuli and the less well studied harsh (nociceptive) touch stimuli. First, we measured the relative response thresholds of gentle and harsh touch. Next, we quantified differences in the receptive fields between wild type worms and a mutant with non-functioning posterior touch receptor neurons. We showed that under gentle touch the receptive field of the anterior touch receptor neurons extends into the posterior half of the body. Finally, we found that the behavioral response to gentle touch does not depend on the locomotion of the animal immediately prior to the stimulus, but does depend on the location of the previous touch. Responses to harsh touch, on the other hand, did not depend on either previous velocity or stimulus location. Differences in gentle and harsh touch response characteristics may reflect the different innervation of the respective mechanosensory cells. Our assay will facilitate studies of mechanosensation, sensory adaptation, and nociception.


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