Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes

doi:10.1016/0012-1606(85)90443-9

Developmental Biology

Volume 111, Issue 1, September 1985, Pages 158-170

https://doi.org/10.1016/0012-1606(85)90443-9 Get rights and content

Abstract

Eight pairs of chemosensory neurons in Caenorhabditis elegans take up fluorescein dyes entering through the chemosensory organs. These are amphid neurons ADF, ASH, ASI, ASJ, ASK, and ADL and phasmid neurons PHA and PHB. When filled with dye, the processes and cell bodies of these neurons can be examined in live animals by fluorescence microscopy. Using this technique, we have identified five genes, unc-33, unc-44, unc-51, unc-76, and unc-106, that affect the growth of the amphid and phasmid axons. These genes were found to affect the axons of the mechanosensory PDE neurons as well. The unc-33 mutation specifically affects neuronal microtubules. Sensory dendrites in this mutant have a superabundance of microtubules. Moreover, many of these microtubules are abnormal in diameter, and some form hooks or multiple tubules.

References (29)

D. Bray
Axonal growth in response to experimentally applied mechanical tension
Dev. Biol
(1984)
J.E. Sulston et al.
The Caenorhabditis elegans male: Postembryonic development of nongonadal structures
Dev. Biol
(1980)
J.E. Sulston et al.
Postembryonic cell lineages of the nematode Caenorhabditis elegans
Dev. Biol
(1977)
J.E. Sulston et al.
Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans
Dev. Biol
(1981)
J.E. Sulston et al.
Regulation and cell autonomy during postembryonic development of Caenorhabditis elegans
Dev. Biol
(1980)
J.E. Sulston et al.
The embryonic cell lineage of the nematode Caenorhabditis elegans
Dev. Biol
(1983)
D.G. Albertson et al.
The pharynx of Caenorhabditis elegans
Phil. Trans. R. Soc. London Ser. B
(1976)
D. Bentley et al.
Pathfinding by peripheral pioneer neurons in grasshoppers
Science (Washington, D. C.)
(1982)
D. Bray
Filopodial contraction and growth cone guidance
S. Brenner
The genetics of behavior
Brit. Med. Bull
(1973)

S. Brenner

The genetics of Caenorhabditis elegans

Genetics

(1974)

A. Frohlich et al.

Quantitative features of synapse formation in the fly's visual system. I. The presynaptic photoreceptor terminal

J. Neurosci

(1983)

C.S. Goodman et al.

Pathfinding by neuronal growth cones in grasshopper embryos

C.S. Goodman et al.

Cell recognition during neuronal development in insect embryos

Cited by (361)

Physiological functions of ULK1/2
2024, Journal of Molecular Biology
UNC-51-like kinases 1 and 2 (ULK1/2) are serine/threonine kinases that are best known for their evolutionarily conserved role in the autophagy pathway. Upon sensing the nutrient status of a cell, ULK1/2 integrate signals from upstream cellular energy sensors such as mTOR and AMPK and relay them to the downstream components of the autophagy machinery. ULK1/2 also play indispensable roles in the selective autophagy pathway, removing damaged mitochondria, invading pathogens, and toxic protein aggregates. Additional functions of ULK1/2 have emerged beyond autophagy, including roles in protein trafficking, RNP granule dynamics, and signaling events impacting innate immunity, axon guidance, cellular homeostasis, and cell fate. Therefore, it is no surprise that alterations in ULK1/2 expression and activity have been linked with pathophysiological processes, including cancer, neurological disorders, and cardiovascular diseases. Growing evidence suggests that ULK1/2 function as biological rheostats, tuning cellular functions to intra and extra-cellular cues. Given their broad physiological relevance, ULK1/2 are candidate targets for small molecule activators or inhibitors that may pave the way for the development of therapeutics for the treatment of diseases in humans.
Integration of spatially opposing cues by a single interneuron guides decision-making in C. elegans
2023, Cell Reports
The capacity of animals to respond to hazardous stimuli in their surroundings is crucial for their survival. In mammals, complex evaluations of the environment require large numbers and different subtypes of neurons. The nematode C. elegans avoids hazardous chemicals they encounter by reversing their direction of movement. How does the worms’ compact nervous system process the spatial information and direct motion change? We show here that a single interneuron, AVA, receives glutamatergic excitatory and inhibitory signals from head and tail sensory neurons, respectively. AVA integrates the spatially distinct and opposing cues, whose output instructs the animal’s behavioral decision. We further find that the differential activation of AVA stems from distinct localization of inhibitory and excitatory glutamate-gated receptors along AVA’s process and from different threshold sensitivities of the sensory neurons. Our results thus uncover a cellular mechanism that mediates spatial computation of nociceptive cues for efficient decision-making in C. elegans.
A proton-inhibited DEG/ENaC ion channel maintains neuronal ionstasis and promotes neuronal survival under stress
2023, iScience
The nervous system participates in the initiation and modulation of systemic stress. Ionstasis is of utmost importance for neuronal function. Imbalance in neuronal sodium homeostasis is associated with pathologies of the nervous system. However, the effects of stress on neuronal Na⁺ homeostasis, excitability, and survival remain unclear. We report that the DEG/ENaC family member DEL-4 assembles into a proton-inactivated sodium channel. DEL-4 operates at the neuronal membrane and synapse to modulate Caenorhabditis elegans locomotion. Heat stress and starvation alter DEL-4 expression, which in turn alters the expression and activity of key stress-response transcription factors and triggers appropriate motor adaptations. Similar to heat stress and starvation, DEL-4 deficiency causes hyperpolarization of dopaminergic neurons and affects neurotransmission. Using humanized models of neurodegenerative diseases in C. elegans, we showed that DEL-4 promotes neuronal survival. Our findings provide insights into the molecular mechanisms by which sodium channels promote neuronal function and adaptation under stress.
Microtubule remodelling as a driving force of axon guidance and pruning
2023, Seminars in Cell and Developmental Biology
The establishment of neuronal connectivity relies on the microtubule (MT) cytoskeleton, which provides mechanical support, roads for axonal transport and mediates signalling events. Fine-tuned spatiotemporal regulation of MT functions by tubulin post-translational modifications and MT-associated proteins is critical for the coarse wiring and subsequent refinement of neuronal connectivity. The defective regulation of these processes causes a wide range of neurodevelopmental disorders associated with connectivity defects. This review focuses on recent studies unravelling how MT composition, post-translational modifications and associated proteins influence MT functions in axon guidance and/or pruning to build functional neuronal circuits. We here summarise experimental evidence supporting the key role of this network as a driving force for growth cone steering and branch-specific axon elimination. We further provide a global overview of the MT-interactors that tune developing axon behaviours, with a special emphasis on their emerging versatility in the regulation of MT dynamics/structure. Recent studies establishing the key and highly selective role of the tubulin code in the regulation of MT functions in axon pathfinding are also reported. Finally, our review highlights the emerging molecular links between these MT regulation processes and guidance signals that wire the nervous system.
C. elegans vab-6 encodes a KIF3A kinesin and functions cell non-autonomously to regulate epidermal morphogenesis
2023, Developmental Biology
Cells undergo strict regulation to develop their shape in a process called morphogenesis. Caenorhabditis elegans with mutations in the variable abnormal (vab) class of genes have been shown to display epidermal and neuronal morphological defects. While several vab genes have been well-characterized, the function of the vab-6 gene remains unknown. Here, we show that vab-6 is synonymous with a subunit of the kinesin-II heterotrimeric motor complex called klp-20/Kif3a, a motor well-understood to be involved in developing sensory cilia in the nervous system. We show that certain klp-20 alleles cause animals to develop a bumpy body phenotype that is variable but most severe in mutants containing single amino-acid substitutions in the catalytic head-domain sites of the protein. Surprisingly, animals carrying a klp-20 null allele do not show the bumpy epidermal phenotype suggesting genetic redundancy and only when mutant versions of the KLP-20 protein are present, the epidermal phenotype is observed. The bumpy epidermal phenotype was not observed in other kinesin-2 mutants, suggesting that KLP-20 is functioning independently from its role in intraflagellar transport (IFT) during ciliogenesis. Interestingly, despite having such a prominent epidermal phenotype, KLP-20 is not expressed in the epidermis, strongly suggesting a cell non-autonomous role in which it regulates epidermal morphogenesis.
A developmental pathway for epithelial-to-motoneuron transformation in C. elegans
2022, Cell Reports
Motoneurons and motoneuron-like pancreatic β cells arise from radial glia and ductal cells, respectively, both tube-lining progenitors that share molecular regulators. To uncover programs underlying motoneuron formation, we studied a similar, cell-division-independent transformation of the C. elegans tube-lining Y cell into the PDA motoneuron. We find that lin-12/Notch acts through ngn-1/Ngn and its regulator hlh-16/Olig to control transformation timing. lin-12 loss blocks transformation, while lin-12(gf) promotes precocious PDA formation. Early basal expression of ngn-1/Ngn and hlh-16/Olig depends on sem-4/Sall and egl-5/Hox. Later, coincident with Y cell morphological changes, ngn-1/Ngn expression is upregulated in a sem-4/Sall and egl-5/Hox-dependent but hlh-16/Olig-independent manner. Subsequently, Y cell retrograde extension forms an anchored process priming PDA axon extension. Extension requires ngn-1-dependent expression of the cytoskeleton organizers UNC-119, UNC-44/ANK, and UNC-33/CRMP, which also activate PDA terminal-gene expression. Our findings uncover cell-division-independent regulatory events leading to motoneuron generation, suggesting a conserved pathway for epithelial-to-motoneuron/motoneuron-like cell differentiation.

View all citing articles on Scopus

^☆: Part of this work was supported by NIH Grants NS16510 and NS20258 and Basil O'Connor Research Grant No. 5–f411 from the March of Dimes Foundation to J.C.

View full text

Article preview

Developmental Biology

Abstract

References (29)

Axonal growth in response to experimentally applied mechanical tension

Dev. Biol

The Caenorhabditis elegans male: Postembryonic development of nongonadal structures

Dev. Biol

Postembryonic cell lineages of the nematode Caenorhabditis elegans

Dev. Biol

Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans

Dev. Biol

Regulation and cell autonomy during postembryonic development of Caenorhabditis elegans

Dev. Biol

The embryonic cell lineage of the nematode Caenorhabditis elegans

Dev. Biol

The pharynx of Caenorhabditis elegans

Phil. Trans. R. Soc. London Ser. B

Pathfinding by peripheral pioneer neurons in grasshoppers

Science (Washington, D. C.)

Filopodial contraction and growth cone guidance

The genetics of behavior

Brit. Med. Bull

The genetics of Caenorhabditis elegans

Genetics

Quantitative features of synapse formation in the fly's visual system. I. The presynaptic photoreceptor terminal

J. Neurosci

Pathfinding by neuronal growth cones in grasshopper embryos

Cell recognition during neuronal development in insect embryos

Cited by (361)

Physiological functions of ULK1/2

Integration of spatially opposing cues by a single interneuron guides decision-making in C. elegans

A proton-inhibited DEG/ENaC ion channel maintains neuronal ionstasis and promotes neuronal survival under stress

Microtubule remodelling as a driving force of axon guidance and pruning

C. elegans vab-6 encodes a KIF3A kinesin and functions cell non-autonomously to regulate epidermal morphogenesis

A developmental pathway for epithelial-to-motoneuron transformation in C. elegans

Full paperAxonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes☆

Abstract

Dev. Biol

Dev. Biol

Dev. Biol

Dev. Biol

Dev. Biol

Dev. Biol

The pharynx of Caenorhabditis elegans

Phil. Trans. R. Soc. London Ser. B

Pathfinding by peripheral pioneer neurons in grasshoppers

Science (Washington, D. C.)

Filopodial contraction and growth cone guidance

The genetics of behavior

Brit. Med. Bull

The genetics of Caenorhabditis elegans

Genetics

Quantitative features of synapse formation in the fly's visual system. I. The presynaptic photoreceptor terminal

J. Neurosci

Pathfinding by neuronal growth cones in grasshopper embryos

Cell recognition during neuronal development in insect embryos

Full paper
Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes☆