scholarly journals unc-3, a gene required for axonal guidance in Caenorhabditis elegans, encodes a member of the O/E family of transcription factors

Development ◽  
1998 ◽  
Vol 125 (8) ◽  
pp. 1561-1568 ◽  
Author(s):  
B.C. Prasad ◽  
B. Ye ◽  
R. Zackhary ◽  
K. Schrader ◽  
G. Seydoux ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Motor Neurons ◽  
Gene Mutations ◽  
Axonal Guidance ◽  
Axonal Outgrowth ◽  
E Proteins ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Dauer Formation ◽  
Neuronal Lineage

The expression of specialized signal transduction components in mammalian olfactory neurons is thought to be regulated by the O/E (Olf-1/EBF) family of transcription factors. The O/E proteins are expressed in cells of the olfactory neuronal lineage throughout development and are also expressed transiently in neurons in the developing nervous system during embryogenesis. We have identified a C. elegans homologue of the mammalian O/E proteins, which displays greater than 80% similarity over 350 amino acids. Like its mammalian homologues, CeO/E is expressed in certain chemosensory neurons (ASI amphid neurons) throughout development and is also expressed transiently in developing motor neurons when these cells undergo axonal outgrowth. We demonstrate that CeO/E is the product of the unc-3 gene, mutations in which cause defects in the axonal outgrowth of motor neurons, as well as defects in dauer formation, a process requiring chemosensory inputs. These observations suggest that the O/E family of transcription factors play a central and evolutionarily conserved role in the expression of proteins essential for axonal pathfinding and/or neuronal differentiation in both sensory and motor neurons.

scholarly journals Control of spinal motor neuron terminal differentiation through sustained Hoxc8 gene activity

2021 ◽  
Author(s):  
Catarina Catela ◽  
Yifei Weng ◽  
Kailong Wen ◽  
Weidong Feng ◽  
Paschalis Kratsios
Keyword(s):  
Transcription Factors ◽  
Motor Neurons ◽  
Terminal Differentiation ◽  
Differentiation Markers ◽  
Spinal Motor Neuron ◽  
C Elegans ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Evolutionarily Conserved ◽  
Genes Encoding

Spinal motor neurons (MNs) constitute cellular substrates for several movement disorders. Although their early development has received much attention, how spinal MNs become and remain terminally differentiated is poorly understood. Here, we determined the transcriptome of mouse brachial MNs at embryonic and postnatal stages. We found that genes encoding homeodomain (HOX, LIM) transcription factors (TFs), previously implicated in early MN development, continue to be expressed postnatally, suggesting later functions. To test this, we inactivated Hoxc8 at successive stages of MN development. We found that Hoxc8 is not only required to establish but also maintain expression of several MN terminal differentiation markers. Furthermore, we uncovered novel TFs with continuous MN expression, a Hoxc8 dependency for maintained expression of Iroquois (Irx) homeodomain TFs, and a new role for Irx2 in MN development. Our findings dovetail recent observations in C. elegans MNs, pointing toward an evolutionarily conserved role for Hox in neuronal terminal differentiation.

scholarly journals Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function

2020 ◽  
Author(s):  
Yinan Li ◽  
Anthony Osuma ◽  
Edgar Correa ◽  
Munachiso A. Okebalama ◽  
Pauline Dao ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Genome Engineering ◽  
Life Stages ◽  
C Elegans ◽  
Neuronal Identity ◽  
Protein Classes ◽  
Selector Function

ABSTRACTTerminal selectors are transcription factors (TFs) that establish during development and maintain throughout life post-mitotic neuronal identity. We previously showed that UNC-3/Ebf, the terminal selector of C. elegans cholinergic motor neurons (MNs), acts indirectly to prevent alternative neuronal identities (Feng et al., 2020). Here, we globally identify the direct targets of UNC-3. Unexpectedly, we find that the suite of UNC-3 targets in MNs is modified across different life stages, revealing “temporal modularity” in terminal selector function. In all larval and adult stages examined, UNC-3 is required for continuous expression of various protein classes (e.g., receptors, transporters) critical for MN function. However, only in late larvae and adults, UNC-3 is required to maintain expression of MN-specific TFs. Minimal disruption of UNC-3’s temporal modularity via genome engineering affects locomotion. Another C. elegans terminal selector (UNC-30/Pitx) also exhibits temporal modularity, supporting the potential generality of this mechanism for the control of neuronal identity.

scholarly journals Excitatory motor neurons are local oscillators for backward locomotion

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Shangbang Gao ◽  
Sihui Asuka Guan ◽  
Anthony D Fouad ◽  
Jun Meng ◽  
Taizo Kawano ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Oscillatory Activity ◽  
Intrinsic Activity ◽  
Chemical Synapse ◽  
C Elegans ◽  
Cell Ablation ◽  
State Dependent ◽  
Evolutionarily Conserved ◽  
Dependent Inhibition ◽  
Descending Interneurons

Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: (1) forward and backward locomotion is driven by different oscillators; (2) the cholinergic and excitatory A-class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive backward locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high-voltage-activated calcium current underlies A motor neuron’s oscillation; (4) descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron’s intrinsic activity to regulate backward locomotion. Thus, motor neurons themselves derive rhythms, which are dually regulated by the descending interneurons to control the reversal motor state. These and previous findings exemplify compression: essential circuit properties are conserved but executed by fewer numbers and layers of neurons in a small locomotor network.

scholarly journals Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yinan Li ◽  
Anthony Osuma ◽  
Edgar Correa ◽  
Munachiso A Okebalama ◽  
Pauline Dao ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Genome Engineering ◽  
Life Stages ◽  
C Elegans ◽  
Neuronal Identity ◽  
Protein Classes ◽  
Selector Function

Terminal selectors are transcription factors (TFs) that establish during development and maintain throughout life post-mitotic neuronal identity. We previously showed that UNC-3/Ebf, the terminal selector of C. elegans cholinergic motor neurons (MNs), acts indirectly to prevent alternative neuronal identities (Feng et al., 2020). Here, we globally identify the direct targets of UNC-3. Unexpectedly, we find that the suite of UNC-3 targets in MNs is modified across different life stages, revealing ‘temporal modularity’ in terminal selector function. In all larval and adult stages examined, UNC-3 is required for continuous expression of various protein classes (e.g. receptors, transporters) critical for MN function. However, only in late larvae and adults, UNC-3 is required to maintain expression of MN-specific TFs. Minimal disruption of UNC-3’s temporal modularity via genome engineering affects locomotion. Another C. elegans terminal selector (UNC-30/Pitx) also exhibits temporal modularity, supporting the potential generality of this mechanism for the control of neuronal identity.

scholarly journals A directional 3D neurite outgrowth model for studying motor axon biology and disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xandor M. Spijkers ◽  
Svetlana Pasteuning-Vuhman ◽  
Jennifa C. Dorleijn ◽  
Paul Vulto ◽  
Nienke R. Wevers ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Microtiter Plate ◽  
Axonal Guidance ◽  
Immunofluorescent Staining ◽  
Axonal Outgrowth ◽  
Dependent Manner ◽  
Laboratory Equipment ◽  
Motor Neuron Diseases ◽  
Adjacent Layer

AbstractWe report a method to generate a 3D motor neuron model with segregated and directed axonal outgrowth. iPSC-derived motor neurons are cultured in extracellular matrix gel in a microfluidic platform. Neurons extend their axons into an adjacent layer of gel, whereas dendrites and soma remain predominantly in the somal compartment, as verified by immunofluorescent staining. Axonal outgrowth could be precisely quantified and was shown to respond to the chemotherapeutic drug vincristine in a highly reproducible dose-dependent manner. The model was shown susceptible to excitotoxicity upon exposure with excess glutamate and showed formation of stress granules upon excess glutamate or sodium arsenite exposure, mimicking processes common in motor neuron diseases. Importantly, outgrowing axons could be attracted and repelled through a gradient of axonal guidance cues, such as semaphorins. The platform comprises 40 chips arranged underneath a microtiter plate providing both throughput and compatibility to standard laboratory equipment. The model will thus prove ideal for studying axonal biology and disease, drug discovery and regenerative medicine.

scholarly journals Early loss of Scribble affects cortical development and interhemispheric connectivity resulting in psychomotor dysregulation

2019 ◽  
Author(s):  
Jerome Ezan ◽  
Maité M. Moreau ◽  
Tamrat M. Mamo ◽  
Miki Shimbo ◽  
Maureen Decroo ◽  
...  
Keyword(s):  
Planar Cell Polarity ◽  
Gene Mutations ◽  
Axonal Guidance ◽  
Activity Impairment ◽  
Mouse Mutants ◽  
Interhemispheric Connectivity ◽  
Evolutionarily Conserved ◽  
Early Brain Development ◽  
And Behavior ◽  
The Impact

AbstractNeurodevelopmental disorders arise from combined defects in processes including cell proliferation, differentiation, migration and commissure formation. The evolutionarily conserved tumor-suppressor protein Scribble (Scrib) serves as a nexus to transduce signals for the establishment of apicobasal and planar cell polarity during these processes. Human SCRIB gene mutations are associated with neural tube defects and this gene is located in the minimal critical region deleted in the rare Verheij syndrome. In this study, we generated brain-specific conditional cKO mouse mutants and assessed the impact of the Scrib deletion on brain morphogenesis and behavior. We showed that embryonic deletion of Scrib in the telencephalon leads to cortical thickness reduction (microcephaly) and alteration of interhemispheric connectivity (corpus callosum and hippocampal commissure agenesis). We correlated these phenotypes with the identification of novel roles for Scrib, both cell- and non-cell-autonomous, on neuronal migration and axonal guidance respectively. Finally, we show that Scrib cKO mice have psychomotor deficits such as locomotor activity impairment and memory alterations. Altogether, we show that Scrib is essential for early brain development and that the outcomes of its brain-specific disruption support a direct or indirect participation of Scrib to neurodevelopmental pathologies.

The Caenorhabditis elegans odr-2 Gene Encodes a Novel Ly-6-Related Protein Required for Olfaction

Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 211-224 ◽  
Author(s):  
Joseph H Chou ◽  
Cornelia I Bargmann ◽  
Piali Sengupta
Keyword(s):  
Caenorhabditis Elegans ◽  
Motor Neurons ◽  
Amino Terminus ◽  
Signaling Proteins ◽  
Related Protein ◽  
Olfactory Neurons ◽  
Unique Role ◽  
C Elegans ◽  
Founding Member ◽  
High Concentrations

Abstract Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.

scholarly journals Glycosylation in Axonal Guidance

2021 ◽  
Vol 22 (10) ◽  
pp. 5143
Author(s):  
Sampada P. Mutalik ◽  
Stephanie L. Gupton
Keyword(s):  
Neuronal Development ◽  
Axonal Guidance ◽  
Axonal Outgrowth ◽  
Axonal Pathfinding ◽  
Guidance Cues ◽  
Functional Implications ◽  
Protein Functions ◽  
Guidance Receptors ◽  
Surface Localization

How millions of axons navigate accurately toward synaptic targets during development is a long-standing question. Over decades, multiple studies have enriched our understanding of axonal pathfinding with discoveries of guidance molecules and morphogens, their receptors, and downstream signalling mechanisms. Interestingly, classification of attractive and repulsive cues can be fluid, as single guidance cues can act as both. Similarly, guidance cues can be secreted, chemotactic cues or anchored, adhesive cues. How a limited set of guidance cues generate the diversity of axonal guidance responses is not completely understood. Differential expression and surface localization of receptors, as well as crosstalk and spatiotemporal patterning of guidance cues, are extensively studied mechanisms that diversify axon guidance pathways. Posttranslational modification is a common, yet understudied mechanism of diversifying protein functions. Many proteins in axonal guidance pathways are glycoproteins and how glycosylation modulates their function to regulate axonal motility and guidance is an emerging field. In this review, we discuss major classes of glycosylation and their functions in axonal pathfinding. The glycosylation of guidance cues and guidance receptors and their functional implications in axonal outgrowth and pathfinding are discussed. New insights into current challenges and future perspectives of glycosylation pathways in neuronal development are discussed.

scholarly journals C. elegans discriminates colors to guide foraging

Science ◽  
2021 ◽  
Vol 371 (6533) ◽  
pp. 1059-1063 ◽  
Author(s):  
D. Dipon Ghosh ◽  
Dongyeop Lee ◽  
Xin Jin ◽  
H. Robert Horvitz ◽  
Michael N. Nitabach
Keyword(s):  
Stress Response ◽  
Cellular Stress ◽  
Color Discrimination ◽  
Cellular Stress Response ◽  
Blue Pigment ◽  
Natural Environments ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Foraging Decisions ◽  
Light Guides

Color detection is used by animals of diverse phyla to navigate colorful natural environments and is thought to require evolutionarily conserved opsin photoreceptor genes. We report that Caenorhabditis elegans roundworms can discriminate between colors despite the fact that they lack eyes and opsins. Specifically, we found that white light guides C. elegans foraging decisions away from a blue-pigment toxin secreted by harmful bacteria. These foraging decisions are guided by specific blue-to-amber ratios of light. The color specificity of color-dependent foraging varies notably among wild C. elegans strains, which indicates that color discrimination is ecologically important. We identified two evolutionarily conserved cellular stress response genes required for opsin-independent, color-dependent foraging by C. elegans, and we speculate that cellular stress response pathways can mediate spectral discrimination by photosensitive cells and organisms—even by those lacking opsins.

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