#signaling pathway

Paracrine Factor

Which of the following statements about FGF signaling is FALSE?

FGF signaling is canonical RTK pathway central to embryogenesis requiring heparan sulfate proteoglycan cofactor for high affinity. FGFR dimerization activates FRS2 adaptor and downstream Ras-ERK, PI3K-AKT, PLCγ-STAT cascades controlling proliferation. In limb, FGF10 from mesenchyme induces FGF8 in apical ectodermal ridge which maintains Sonic Hedgehog in zone of polarizing activity via Formin-Gremlin loop, but Sonic Hedgehog protein does not biochemically activate FGF receptors; interaction occurs via transcriptional regulation maintaining FGF expression, not direct receptor phosphorylation. Thus claiming direct activation misrepresents hierarchy. FGFs indeed function through receptor tyrosine kinases and participate in limb outgrowth and segmentation clock.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 18: Limb feedback loop FGF in AER and Shh in ZPA interaction.

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Paracrine Factor

Which of the following proteins is NOT involved in the Hedgehog signaling pathway?

Hedgehog pathway core components include secreted cholesterol-modified ligand Hedgehog, twelve-pass receptor Patched with sterol sensing domain, seven-pass transducer Smoothened homologous to Frizzled GPCR, transcription factor Gli/Ci with five zinc fingers, suppressor Sufu sequestering Gli, and Kif7 kinesin. Upon activation, Smoothened accumulates in primary cilium membrane blocking proteolytic cleavage of Gli into repressor GliR, generating activator GliA driving targets Patched, Hhip. LRP5/6 is single-pass Wnt co-receptor binding Wnt with Frizzled, recruiting Axin, stabilizing beta-catenin for TCF activation. LRP not involved in Hedgehog binding or transduction, distinguishing pathway specificity for patterning and growth.

Ref: Varjosalo & Taipale, Genes & Development 2008: Hedgehog pathway components - Patched, Smoothened, Gli; LRP excluded.

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Paracrine Factor

Which protein acts as an intracellular transducer in the BMP signaling pathway?

BMP receptors are serine/threonine kinase family phosphorylating receptor-regulated Smads Smad1,5,8 upon BMP2/4 binding to ALK2/3/6 type I and BMPR2 type II. Phosphorylated Smad1/5/8 complexes with Co-Smad Smad4, translocates to nucleus via importin beta binding MH2 domain to activate Id1-3, Msx1/2 transcription factors patterning ventral mesoderm and inhibiting neurogenesis by repressing Sox2. STAT proteins transduce JAK cytokine signaling via tyrosine phosphorylation and dimerization, JAK is cytoplasmic tyrosine kinase, beta-catenin transduces Wnt via TCF/LEF. Thus Smad proteins canonical intracellular transducers distinguishing TGF-beta/BMP pathway from RTK and GPCR signaling logic for dorsoventral patterning.

Ref: Heldin et al., Nature 1997: Smad proteins transduce TGF-beta and BMP signaling to nucleus.

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C-Elegans Development-l

Which signaling pathway regulates EMS cell fate in response to P2 signaling?

EMS fate specification integrates Wnt signaling from neighbor P2 historically termed Wnt/MAPK or Wnt/beta-catenin asymmetry pathway. MOM-2 Wnt produced by P2 signals via MOM-5 Frizzled, MOM-4 TAK1 MAPKKK, WRM-1 beta-catenin, LIT-1 Nemo-like kinase to EMS, activating MAPK-like cascade depleting nuclear POP-1 TCF from posterior daughter E via phosphorylation-triggered export. Low POP-1 converts from repressor to activator enabling END-1,3 expression and gut differentiation. Notch pathway distinguishes AB fate, but EMS specification relies primarily on Wnt asymmetry. Genetic removal of mom genes converts E to MS.

Ref: Rocheleau et al., Cell 1997: Wnt signaling via WRM-1 and LIT-1 regulates EMS fate in response to P2.

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C-Elegans Development-l

Which pathway is required for distinguishing ABa and ABp cells?

Early C. elegans embryo distinguishes AB daughters ABa and ABp via Notch signaling integrating cell contact geometry and timing. At four-cell stage, P2 expresses APX-1 Delta ligand contacting ABp but not ABa due to spatial arrangement and spindle orientation governed by PAR polarity. APX-1 binds GLP-1 Notch receptor on ABp, gamma-secretase cleavage releases intracellular domain that activates lag-1 transcription factor and bHLH repressors ref-1 family. This induces distinct transcriptomes; ABa generates anterior pharynx and neurons while ABp generates dorsal posterior structures. Without GLP-1-APX-1 both adopt ABa-like fate.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 8: Notch signaling distinguishes ABa and ABp via GLP-1 and APX-1.

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C-Elegans Development-l

Which signaling pathway is responsible for vulva induction in C. elegans?

Vulval induction relies on conserved RTK/Ras/MAPK cascade downstream of anchor cell EGF signal. Anchor cell in somatic gonad secretes LIN-3 EGF-like ligand, which binds LET-23 EGFR homolog on vulval precursors P5.p-P7.p, localized basolaterally by LIN-2, LIN-7, LIN-10 scaffolding complex. Activated LET-23 recruits SEM-5 Grb2 adaptor, LET-60 Ras, LIN-45 Raf, MEK-2 kinase and MPK-1 ERK, phosphorylating transcription factors LIN-1 ETS and LIN-31 forkhead. Highest LIN-3 concentration near P6.p specifies primary vulval fate, while lateral LIN-12 Notch ligands from P6.p drive secondary fates in neighbors, ensuring precise three-cell patterning and morphogenesis.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 8: Vulval induction - RTK/Ras/MAPK pathway and LIN-3 signaling.

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Elegans -ll

Which pathway is involved in EMS fate specification?

EMS polarity relies heavily on Wnt signaling from P2. P2 expresses MOM-2 Wnt ligand and MOM-5 Frizzled, activating both canonical Wnt/beta-catenin asymmetry pathway and Src/MES-1 pathway in EMS. MOM-2 binding causes WRM-1 beta-catenin nuclear accumulation in E but not MS, along with reduction of POP-1 TCF, converting POP-1 to transcriptional activator with SYS-1 beta-catenin to induce end-1, end-3 endoderm genes. Mutations in mom-2, mom-5, wrm-1 cause both EMS daughters to become MS-like. Therefore EMS fate specification uses Wnt signal to establish E versus MS asymmetry downstream of initial SKN-1 competence input.

Ref: Rocheleau et al. 1997; Gilbert Chapter 4: Wnt pathway involved in EMS fate specification via MOM-2.

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Eye Lens Induction -l

Which of the following factors is activated by FGF8 in eye lens induction?

FGF8 secreted by optic vesicle neuroepithelium acts as second-phase inducer after BMP priming. Vogel-Hopker experiments demonstrated FGF8 transcripts localize to distal optic vesicle, and beads soaked in FGF8 implanted under head ectoderm ectopically activate L-Maf, a large Maf bZIP transcription factor specific to lens. L-Maf directly binds LCE enhancer of delta-crystallin and transactivates lens fiber differentiation genes including Prox1 and connexins. Inhibiting FGFR signaling with dominant-negative receptor abolishes L-Maf expression, proving FGF8 initiates transcriptional cascade for fiber elongation and crystallin accumulation.

Ref: PMCID PMC article: The Function of FGF Signaling in the Lens Placode - FGF8 induction of L-Maf expression.

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Limb Development -l

Which signaling pathway primarily regulates the dorsal-ventral patterning of limbs?

Dorsal-ventral limb patterning determining dorsal nail, hair, and extensor versus ventral pad, sole, and flexor fates is regulated by Wnt7a secreted from dorsal ectoderm. Wnt7a induces LMX1B transcription factor in dorsal mesenchyme imposing dorsal characteristics, while ventral ectoderm expresses Engrailed-1 which represses Wnt7a ventrally permitting ventral identity. Sonic hedgehog governs anterior-posterior axis, BMP promotes ventral ectoderm and interdigital apoptosis, FGF10 initiates budding. Wnt7a knockout transforms dorsal into ventral, yielding double-ventral bi-ventral limbs with footpads dorsally and absent nails. Conserved across chick mouse human models, this mechanism illustrates classic embryological principles integrated with modern molecular genetics.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Dorsoventral patterning – Wnt7a and Lmx1b dorsal specification.

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Regeneration -l

What role does the Erk signaling pathway play in planarian regeneration?

Wound-induced ERK mitogen-activated protein kinase signaling is activated within minutes after injury via ROS, calcium, and EGFR signals. Phosphorylated ERK initially appears at both wound faces but becomes sustained selectively at anterior-facing wounds where it drives transcription of anterior pole genes including notum, follistatin, and foxD. ERK inhibition by MEK inhibitor U0126 abolishes notum induction leading to tail duplication at anterior wounds, while tail regeneration relatively preserved. Thus Erk promotes head formation by inducing anti-Wnt program rather than inhibiting tail regeneration directly, activating upstream wound response, not Wnt itself, and suppressing posterior genes through Notum upregulation.

Ref: Development, Fraguas et al.: ERK signaling promotes anterior regeneration and induces notum in planaria.

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