TABLE 6-3 Various Uses of Signaling Pathways in Vertebrate Development

Pathway

Use

Wnt pathway

Dorsalization of the body (fish, frogs) induction of the organizer or node; posteriorization of the neural plate, midbrain development; dermamyotome induction, somite dorsoventral organization; dorsalization of the fin or limb; female reproductive development; kidney development; dorsoventral differences of limb, hematopoiesis

Transforming growth factor β pathway (BMP,TGFβ, GDF, VEGR, Nodal, Activin, Dorsalin)

Mesoderm induction; induction of organizer, left-right asymmetry; ventralization of mesoderm and ectoderm; neural-crest development to neurons; chondrogenesis of limb, bone development; digit-web spacing, tooth, heart; notochord induction of floor plate of neural tube; notochord and floor-plate induction of sclerotome of somite; prechordal mesoderm induction of prosencephalon; left-right asymmetry, somitogenesis, lung; fin or limb development; zone-of-polarizing-activity (ZPA) induction of anteroposterior axis; gut and visceral mesoderm, hair follicle, skin, and tooth development; spermatogenesis

Hedgehog pathway (Sonic, Indian, Desert)

Notochord induction of floor plate of neural tube; notochord and floor-plate induction of sclerotome of somite and the dorsoventral organization of neural tube; prechordal mesoderm induction of prosencephalon; inhibit cyclopia; ZPA induction of anteroposterior axis of fin or limb development; gut and visceral mesoderm development; hair development

Receptor tyrosine kinase pathway (EGF, FGF, PDGF, EPH)

Mesoderm maintenance; limb (apical ectodermal ridge), vasculogenesis; hair follicle, inner ear, retinotectal projection; astrocyte differentiation, branchial arch signal to neural crest; heart, lung, and tooth development

Notch-Delta pathway (Delta, Serrate, Jagged)

Several steps of neurogenesis; oligodendrocyte differentiation, retina development; somitogenesis, inner-ear development; feather-bud development; blood-cell development (e.g., thymocytes)

Note: These pathways are used repeatedly in early development. The particular uses in developmental processes are well conserved across vertebrates.

As shown in Table 6-4 and Table 6-5, many single-null mutants of the mouse are born live and have minimal defects that can be scored as developmental defects (e.g., skeletal abnormalities). Some have motor coordination defects, such as the WNT1 null mutant, which lacks the entire cerebellum. Some live for a few days, and others reach adulthood and are fertile. In Table 6-4, five pathways are surveyed partially (one or two components eliminated per pathway). In Table 6-5, one pathway is surveyed exhaustively (all components eliminated one at a time). Each kind of mutant is defective for one component of one signaling



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