🪱 A Transparent Window into Biology: C. elegans Primer

🌍 Introduction

• Sydney Brenner (1960s) chose C. elegans as a model to study development + nervous system.
• Now: over 1000 labs study it, with ~1200 papers/year!
• Why so powerful? Tiny size, transparency, fast life cycle, easy genetics, and similarity to humans (40% of human disease genes have worm orthologs).

🧬 Basics

• Size: L1 larvae ~0.25 mm, adults ~1 mm.
• Life cycle: egg → 4 larval stages (L1–L4) → adult in ~3 days at 25 °C.
• Dauer stage: survival form under stress, with protective cuticle and mouth plug. Dauer can last months and disperse to new habitats.
• Food: bacteria (E. coli in lab, rotting fruit in wild).
• Maintenance: cheap, grows on agar, can be frozen for years.

⚧ Sexual Forms

• Two types:
  • Hermaphrodites (XX): self-fertilize, produce sperm first, then oocytes. Up to 300 progeny alone, ~1000 with male help.
  • Males (XO): rare (~0.2%), used for genetic exchange.
• Sex determined by X:autosome ratio.
• Selfing = simplified genetics, easy stock keeping.

🧪 Genetics

• Famous for forward genetics (find mutants → identify gene) and reverse genetics (target a known gene).
• Classic mutagen: EMS → point mutations.
• Now: CRISPR/Cas9 editing, RNAi feeding, whole genome sequencing, million mutation project.
• Can freeze mutant strains and recover later.
• Nomenclature: genes italic (mec-7), proteins caps (MEC-7), phenotypes capitalized (Unc = uncoordinated).

💡 Why Choose C. elegans?

• ✅ Transparent → see cells & proteins in vivo.
• ✅ Invariant cell lineage → fate of all ~959 somatic cells mapped.
• ✅ Short generation, big brood size.
• ✅ Safe (can’t grow in humans).
• ✅ Tools: GFP reporters, optogenetics, calcium sensors, microfluidics.
• Resources: WormBase, WormBook, WormAtlas.

🧫 Tissues

• Epidermis (skin): makes cuticle, models ECM, wound healing, and innate immunity. Mutations → Dumpy (Dpy), Roller (Rol), Blister (Bli).
• Muscles: 95 body wall cells, oblique striations. Mutants → Unc (uncoordinated). Insights into muscular dystrophy.
• Digestive system: pharynx grinds food, intestine (20 cells). Used to study organogenesis, FoxA/pha-4, and pathogen infections.
• Nervous system: 302 neurons in hermaphrodite, 383 in males. First complete connectome! Uses neurotransmitters like ACh, GABA, dopamine. Behaviors: chemotaxis, thermotaxis, learning, “sleep-like” lethargus.
• Reproductive system: Hermaphrodites = 2 gonad arms; males = 1. Sex-specific anatomy (vulva vs. fan-tail). Models for stem cells, meiosis, and signaling pathways (Notch, Ras, Wnt).

📜 Genome

• First multicellular organism sequenced (1998).
• Genome: ~100 Mb, ~20,400 protein-coding genes.
• Organized into 6 chromosomes (I–V + X).
• Special features:
  • Trans-splicing (SL1/SL2 leader sequences).
  • Operons (like bacteria).
  • Mostly small introns.
• Holocentric chromosomes (spindle attaches all along).

🌱 Ecology & Evolution

• Found in rotting vegetation, compost, fruit—not plain soil.
• Survive as dauer larvae in the wild, can “nictate” (stand up & wave) to hitch rides on insects.
• Belongs to Nematoda → Ecdysozoa (closer to flies than to earthworms).
• Related nematodes: free-living + parasitic (human diseases, crop pests, animal parasites).
• C. elegans research helps understand parasites and drug resistance.

🏆 Key Discoveries

• 1970s–2000s:
  • Apoptosis genes (ced-3, ced-4, ced-9 → conserved in humans).
  • Notch, Ras signaling.
  • microRNAs (lin-4) discovered here first.
  • RNAi discovered (Nobel Prize 2006).
  • GFP as a marker (Nobel Prize 2008).
  • Full cell lineage + connectome mapped.
  • Genes regulating aging (insulin pathway, daf-2 → doubled lifespan).

👩‍🔬 Community

• C. elegans research culture = highly collaborative.
• Worm Breeder’s Gazette, WormBase, and CGC (genetics center) share resources freely.
• Conferences and WormBook keep knowledge open.

🔮 Future Directions

• Genome-wide CRISPR knockouts.
• More regulatory RNA discoveries.
• Whole-nervous-system function with optogenetics.
• Insights into aging, host–pathogen interactions, ecology, and synthetic biology.