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#signaling molecule

13 public questions tagged with this topic.

Induction Morphogen -ll

Which signaling molecule is responsible for specifying neural tube patterning along the dorsal-ventral axis?

Ventral neural tube identity is controlled by Sonic hedgehog secreted from notochord and floor plate. Shh diffuses dorsally establishing a ventral-to-dorsal gradient that antagonizes dorsal BMP and Wnt signals from roof plate. Different thresholds activate graded transcription factor codes: high Shh induces Nkx2.2 and floor plate genes, intermediate induces Olig2 and motor neurons, low induces Pax6 and interneurons. Gli activator-repressor ratio translates Shh dose into position-specific gene expression, compartmentalizing motor neuron, V0-V3 interneuron domains along dorsoventral axis essential for functional spinal cord circuitry and locomotor output.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 13: Neural Tube Dorsoventral Patterning by Shh.

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Induction Morphogen -ll

Which of the following is an example of a morphogen?

Sonic hedgehog is quintessential secreted morphogen modified with cholesterol and palmitate moieties, diffusing to form ventral-to-dorsal gradient in vertebrate neural tube and posterior-to-anterior gradient in limb bud. Concentration-dependent activation of Gli transcription factor family specifies floor plate at highest levels, motor neurons at intermediate Olig2 threshold and distinct interneuron classes at progressively lower thresholds. Mutations in Shh cause holoprosencephaly and limb malformations, confirming essential patterning role. Unlike cytoskeletal proteins or polymerases, Shh satisfies criteria of long-range signaling, threshold-dependent fate specification and direct influence on differential gene expression, embodying classic morphogen functionality.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 13: Sonic Hedgehog as Vertebrate Morphogen.

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Induction Morphogen -ll

What is a key characteristic of a morphogen?

Morphogen is defined as secreted signaling molecule that forms concentration gradient from localized source and elicits distinct cellular outcomes at different thresholds, thereby providing positional information across field. Source secretes ligand such as Activin, Sonic hedgehog or Bicoid that diffuses away, creating decreasing concentration with distance. Cells measure ambient dose via receptor occupancy, translating into graded intracellular pathway activation like phosphorylated Smad levels, leading to differential gene expression programs. Long-range action over many cell diameters distinguishes morphogens from short-range paracrine factors, allowing single signal to organize entire tissue proportionally and coordinate patterning according to French flag paradigm.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 4: Morphogen Definition and Long-Range Gradient Action.

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C-Elegans Development-l

Which signaling molecule helps distinguish MS and E lineages in EMS blastomere?

EMS blastomere division into MS mesoderm and E endoderm requires polarized Wnt signaling from P2 integrating cell polarity. P2 secretes MOM-2 Wnt, MOM-5 Frizzled, MES-1 immunoglobulin transmembrane signals activating Wnt/beta-catenin asymmetry pathway: WRM-1 beta-catenin, LIT-1 Nemo-like kinase and KIN-19 phosphorylate POP-1 TCF, exporting it from E nucleus via WRM-1 complex and reducing nuclear level. Low POP-1 plus high SKN-1 allows MED-1/2 and END-1/3 expression specifying endoderm in E, while high POP-1 in MS represses endoderm and promotes mesoderm genes tbx-35.

Ref: Thorpe et al., Cell 1997: MOM-2 Wnt signaling distinguishes MS and E fates downstream of EMS.

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Elegans -ll

Which signaling molecule from P2 influences ABp fate?

At 4-cell stage, dorsal ABp and ventral EMS-P2 contacts establish ABa versus ABp asymmetry. P2 presents Delta-like ligands APX-1 and LAG-2, which bind GLP-1 Notch receptor highly expressed on ABp membrane, owing to par-3 mediated receptor localization. GLP-1 activation cleaves intracellular domain, activating Notch targets in ABp and repressing ABa-specific genes. Thus GLP-1 functions as instructive receptor transducing P2 positional information. Ablation of P2 or glp-1 mutants cause ABp to adopt ABa fate, producing symmetrical pharynx pattern, confirming Notch-mediated signaling from P2 determines dorsal-ventral distinction of AB lineage.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 4: GLP-1 Notch signaling from P2 influences ABp fate.

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Limb Development -l

Which signaling molecule is required for initiating hindlimb development?

Hindlimb initiation and distal patterning integrate Tbx4-Pitx1 selector program with posterior Hox inputs. While Tbx4 and Pitx1 are primary determinants imposing leg identity, posterior distal Hox genes such as Hoxd13 reinforce hindlimb autopod expansion, digit morphogenesis, and maintenance of hindlimb-specific enhancers downstream of Pitx1. Pitx1 activates Tbx4 and represses forelimb program, FGF10 initiates outgrowth, Tbx5 marks forelimb. Among provided choices, Hoxd13 represents distal hindlimb patterning component linked to hindlimb stylization, consistent with its posterior-restricted function in leg morphogenesis and digit development.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Hindlimb development – Pitx1, Tbx4 and distal Hox13 patterning.

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Limb Development -l

Which signaling molecule is secreted from ZPA and regulates digit identity?

Digit identity along anterior-posterior axis is specified by Sonic hedgehog secreted from zone of polarizing activity at posterior border. SHH forms diffusible gradient anteriorly interpreted by Gli3 processing: high SHH posteriorly blocks Gli3 cleavage into repressor, elevating Gli activator specifying digits 5 and 4, while anterior low SHH allows Gli3 repressor specifying digit 1. FGF8 drives distal proliferation, BMP4 mediates interdigital apoptosis, Wnt3a initiates ridge. SHH simultaneously sustains apical ridge via induction of Gremlin1 that antagonizes BMP, coupling patterning with outgrowth maintenance and survival.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: ZPA sonic hedgehog gradient and digit patterning.

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Limb Development -l

Which signaling molecule is required for AER maintenance?

Apical ectodermal ridge at the distal margin secretes fibroblast growth factors maintaining underlying progress zone mesenchyme in proliferative undifferentiated state essential for proximodistal elongation. Induction of ridge requires Wnt3a through beta-catenin activation, while sustained maintenance depends on reciprocal signaling with mesodermal FGF10. Core maintenance molecule produced by ridge itself is FGF8, complemented by FGF4, FGF9, and FGF17. Loss of FGF8 leads to rapid ridge involution, distal apoptosis, and truncation. FGF10 resides in mesenchyme, SHH in posterior ZPA supporting loop via Gremlin antagonism of BMP.

Ref: Alberts, Molecular Biology of the Cell, Chapter 22: Limb development – AER FGF8 maintenance loop.

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Limb Development -ll

Which signaling molecule is required for AER maintenance and limb bud outgrowth?

Sustained limb outgrowth requires continuous FGF8 from apical ectodermal ridge acting on distal mesenchyme. FGF8 activates ERK MAPK and AKT pathways maintaining expression of FGF10, Gremlin and Msx2 in progress zone, preserving proliferation, preventing premature differentiation, and enabling progressive distal specification through Hox activation. Genetic ablation of Fgf8 in mouse AER causes hypoplastic limbs lacking distal elements but forming stylopod proximally. Replacement with FGF8-soaked beads rescues after AER removal, restoring outgrowth and skeletal pattern. Wnt3a induces AER initially, FGF10 induces FGF8, RA antagonizes FGF.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: FGF8 requirement for AER maintenance.

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Limb Development -lll

Which signaling molecule is critical for preventing premature AER regression?

AER persistence depends on balanced BMP antagonism protecting ridge from involution. BMP2 BMP4 BMP7 from mesenchyme and AER itself promote AER regression and induce apoptosis through upregulation of Dkk and activation of Smad signaling antagonizing FGF. Gremlin1 secreted by distal mesenchyme under combined SHH and FGF control binds and sequesters BMP ligands, protecting AER from premature involution. Loss of Gremlin causes early BMP activity elevation, early AER flattening, reduced FGF8 expression, and truncated distal skeleton. Wnt7a dorsalizes, Lmx1b dorsalizes mesenchyme, BMP4 itself would accelerate regression.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: Gremlin prevents premature AER regression.

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Limb Development -lll

Which of the following signaling molecules primarily maintains mesenchymal proliferation beneath the AER?

FGF8 secreted by the apical ectodermal ridge acts as the principal mitogen for the underlying progress zone mesenchyme. It sustains high proliferation, prevents premature chondrogenic differentiation, preserves distal positional value, and drives continuous proximal-distal outgrowth. Surgical AER removal eliminates FGF8 and produces distal truncation, a defect fully rescued by exogenous FGF8 beads restoring MAPK signaling. A positive epithelial-mesenchymal loop operates where mesenchymal FGF10 induces AER FGF8, which in turn maintains FGF10 and Gremlin. Wnt7a dorsalizes, BMP4 promotes apoptosis, SHH patterns anterior-posterior identity specifically.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: Limb Development - AER FGF8 maintains distal proliferation.

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Regeneration -l

Which signaling molecule promotes tail regeneration and inhibits head formation in planaria?

Anterior-posterior patterning in planarians depends on graded canonical Wnt activity where high activity enforces posterior tail fate and inhibits anterior head fate. Wnt1 and Wnt11-2 expressed at posterior pole by muscle position control genes stabilize beta-catenin activating tailless genes including fzd4, hox4, and wntP2. RNA interference against beta-catenin causes ectopic heads posteriorly, overactivation via APC knockdown causes tails anteriorly. Thus Wnt/beta-catenin promotes tail regeneration and suppresses head identity. FGF10 regulates limb bud outgrowth, Sonic hedgehog patterns limb anterior-posterior digits via ZPA, BMP controls dorsoventral axis, not posterior versus anterior choice in planarian regeneration.

Ref: Petersen and Reddien, PNAS 2008: Wnt/beta-catenin promotes tail regeneration and inhibits head fate in planaria.

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