Genes & Development · 1994 · 795 citations · 54 references
Life SciencesDevelopmental BiologyMolecular BiologyEmbryogenesisEmbryologyGastrulationDevelopmental Cell SignalingEmbryonic PatterningMesoderm SpecificationSomite DevelopmentSomite FormationWnt SignalingAxial Mesoderm FormationDorsal DeterminantsDorsal PatterningEctoderm DevelopmentInductive Embryonic SignalsMesoderm DevelopmentSurface Ectoderm DevelopmentWnt In Embryogenesis
Wnt signaling has been implicated in mesoderm formation, but direct evidence in mammals is lacking. The authors examined expression of 12 mammalian Wnt genes, identified three active during gastrulation, and created a likely null allele of Wnt‑3a by gene targeting. Loss of Wnt‑3a causes loss of caudal somites, notochord disruption, tailbud failure, and dorsal CNS dysmorphology, indicating that Wnt‑3a regulates dorsal mesoderm fate and is required for mesodermal and axial development.
Amphibian studies have implicated Wnt signaling in the regulation of mesoderm formation, although direct evidence is lacking. We have characterized the expression of 12 mammalian Wnt-genes, identifying three that are expressed during gastrulation. Only one of these, Wnt-3a, is expressed extensively in cells fated to give rise to embryonic mesoderm, at egg cylinder stages. A likely null allele of Wnt-3a was generated by gene targeting. All Wnt-3a-/Wnt-3a- embryos lack caudal somites, have a disrupted notochord, and fail to form a tailbud. Thus, Wnt-3a may regulate dorsal (somitic) mesoderm fate and is required, by late primitive steak stages, for generation of all new embryonic mesoderm. Wnt-3a is also expressed in the dorsal CNS. Mutant embryos show CNS dysmorphology and ectopic expression of a dorsal CNS marker. We suggest that dysmorphology is secondary to the mesodermal and axial defects and that dorsal patterning of the CNS may be regulated by inductive signals arising from surface ectoderm.
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