TABLE 6-2 The 17 Intercellular Signaling Pathways

Period During Development

Signaling Pathway Used

Early development (before organogenesis and cytodifferentiation) and later (during growth and tissue renewal)


  1. Wingless-Int pathway

  2. Transforming Growth Factor β (receptor serine and threonine kinase) pathway

  3. Hedgehog pathway

  4. Receptor tryrosine kinase (small G proteins) pathway

  5. Notch-Delta pathway

  6. Cytokine receptor (cytoplasmic tyrosine kinases) pathway (STAT pathway)

Middle and late development (during organogenesis and cytodifferentiation) and later (during growth and tissue renewal)


  1. Interleukin-1-Toll Nuclear Factor-Kappa B pathway

  2. Nuclear hormone receptor pathway

  3. Apoptosis pathway

  4. Receptor phosphotyrosine phosphatase pathway

Larval and adult physiology (after cell types have differentiated)


  1. Receptor guanylate cyclase pathway

  2. Nitric oxide receptor pathway

  3. G-protein coupled receptor (large G proteins) pathway

  4. Integrin pathway

  5. Cadherin pathway

  6. Gap junction pathway

  7. Ligand-gated cation channel pathway

Note: The pathways are shared by most animals (metazoa). Note the six pathways used heavily in the early development of most animals (i.e., at stages before organogenesis and cytodifferentiation begin). Along with those pathways, four more are used in later development in the periods of organogenesis and cytodifferentiation, growth, and tissue renewal. Seven pathways are used mostly in the physiological function of differentiated cells; much of that function also involves signaling. Each pathway is identified by the particular transduction intermediates it contains. Most pathways are unique to metazoa, although components of each are often found in single-celled eukaryotes in other signaling roles, such as pathways of checkpoint control, stress response, infection response, mating, and feeding.

pathway is often not lethal. The mutant is born with a limited abnormality of anatomy and sometimes of behavior. The genetic basis for some of these mouse developmental defects is fully known. In some cases, the mutant mice live to adulthood and reproduce.

Are the signaling pathways less important in vertebrate development than in Drosophila? No, the nonlethality in vertebrates reflects the fact that the pathways have a substantial redundancy of signaling components. It is postulated that early in vertebrate evolution (as jawless fish arose), the genome underwent a quadruplication (Holland et al. 1994). In addition, some genes underwent tandem dupli-

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