Modular Control of Glutamatergic Neuronal Identity in C. elegans by Distinct Homeodomain Proteins

Serrano-Saiz, Esther; Poole, Richard J.; Felton, Terry; Zhang, Feifan; Cruz, Estanisla Daniel De La; Hobert, Oliver

doi:10.1016/j.cell.2013.09.052

Cited by 266 publications

(331 citation statements)

References 70 publications

Supporting

Mentioning

315

Contrasting

Order By: Relevance

“…A role of unc-86 in the differentiation of serotonergic and glutamatergic touch neurons has been described previously (Desai et al, 1988;Duggan et al, 1998;Sze et al, 2002;Serrano-Saiz et al, 2013). We show here that unc-86 also controls the terminal differentiation programs of three distinct cholinergic neuron types.…”

Section: Discussionsupporting

confidence: 82%

“…Apart from our description of unc-86 terminal selector function in the serotonergic NSM neurons, unc-86 had previously been described to broadly affect the terminal differentiation program of other serotonergic (Sze et al, 2002) as well as glutamatergic (Duggan et al, 1998;Serrano-Saiz et al, 2013) neurons. We asked whether unc-86 might affect the terminal differentiation program of neurons that use yet another neurotransmitter system.…”

Section: Both Ttx-3 and Unc-86 Single Mutants Also Show Defects In Domentioning

confidence: 86%

See 1 more Smart Citation

The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types

et al. 2014

Self Cite

View full text Add to dashboard Cite

Transcription factors that drive neuron type-specific terminal differentiation programs in the developing nervous system are often expressed in several distinct neuronal cell types, but to what extent they have similar or distinct activities in individual neuronal cell types is generally not well explored. We investigate this problem using, as a starting point, the C. elegans LIM homeodomain transcription factor ttx-3, which acts as a terminal selector to drive the terminal differentiation program of the cholinergic AIY interneuron class. Using a panel of different terminal differentiation markers, including neurotransmitter synthesizing enzymes, neurotransmitter receptors and neuropeptides, we show that ttx-3 also controls the terminal differentiation program of two additional, distinct neuron types, namely the cholinergic AIA interneurons and the serotonergic NSM neurons. We show that the type of differentiation program that is controlled by ttx-3 in different neuron types is specified by a distinct set of collaborating transcription factors. One of the collaborating transcription factors is the POU homeobox gene unc-86, which collaborates with ttx-3 to determine the identity of the serotonergic NSM neurons. unc-86 in turn operates independently of ttx-3 in the anterior ganglion where it collaborates with the ARID-type transcription factor cfi-1 to determine the cholinergic identity of the IL2 sensory and URA motor neurons. In conclusion, transcription factors operate as terminal selectors in distinct combinations in different neuron types, defining neuron type-specific identity features.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Both Ttx-3 and Unc-86 Single Mutants Also Show Defects In Domentioning

confidence: 86%

The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…To further test this hypothesis, we utilized an eat‐4 ‐mutant background and ectopically expressed EAT‐4 in a pair of nonglutamatergic motor neurons that synapse onto the pharyngeal muscle (the NSMs). Expression of EAT‐4 in a neuron is the defining feature of a glutamatergic neuron (Serrano‐Saiz et al ., 2013) and is therefore expected to be sufficient to cause the loading of glutamate into endogenous synaptic vesicles for release onto the pharyngeal muscle. Furthermore, NSM neurons are not required for the lifespan‐extending effect of NP1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chemical activation of a food deprivation signal extends lifespan

Lucanic

Garrett

et al. 2016

Aging Cell

View full text Add to dashboard Cite

SummaryModel organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug‐like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.

show abstract

“…Kratsios et al, 2012;Serrano-Saiz et al, 2013). These previous studies focused on understanding how the expression of terminal effector genes in a differentiating neuron type are regulated ('bottom-up approach').…”

Section: Sox Genes Are Only Selectively Expressed During Embryonic Nementioning

confidence: 99%

C. elegansSoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types

et al. 2015

Self Cite

View full text Add to dashboard Cite

Neurogenesis involves deeply conserved patterning molecules, such as the proneural basic helix-loop-helix transcription factors. Sox proteins and specifically members of the SoxB and SoxC groups are another class of conserved transcription factors with an important role in neuronal fate commitment and differentiation in various species. In this study, we examine the expression of all five Sox genes of the nematode C. elegans and analyze the effect of null mutant alleles of all members of the SoxB and SoxC groups on nervous system development. Surprisingly, we find that, unlike in other systems, neither of the two C. elegans SoxB genes sox-2 (SoxB1) and sox-3 (SoxB2), nor the sole C. elegans SoxC gene sem-2, is broadly expressed throughout the embryonic or adult nervous system and that all three genes are mostly dispensable for embryonic neurogenesis. Instead, sox-2 is required to maintain the developmental potential of blast cells that are generated in the embryo but divide only postembryonically to give rise to differentiated neuronal cell types. Moreover, sox-2 and sox-3 have selective roles in the terminal differentiation of specific neuronal cell types. Our findings suggest that the common themes of SoxB gene function across phylogeny lie in specifying developmental potential and, later on, in selectively controlling terminal differentiation programs of specific neuron types, but not in broadly controlling neurogenesis.

show abstract

Modular Control of Glutamatergic Neuronal Identity in C. elegans by Distinct Homeodomain Proteins

Cited by 266 publications

References 70 publications

The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types

The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types

Chemical activation of a food deprivation signal extends lifespan

C. elegansSoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types

Contact Info

Product

Resources

About