Mesodermal patterning by an inducer gradient depends on secondary cell-cell communication.
BACKGROUND
Gradients of inducing molecules, or morphogens, could impose pattern on early embryos. Although there are candidates for morphogens in several systems, it is not well understood how cells might translate differences in extracellular inducer concentration into an orderly arrangement of cell types. With this question in mind, we have re-examined mesodermal patterning in Xenopus in response to the secreted growth factor activin. Previous work has shown that activin can initiate the formation of a variety of mesodermal tissues in a concentration-dependent fashion. We have sought to disentangle the roles played by individual cell responses to activin and subsequent interactions among induced cells in producing this outcome.


RESULTS
We find that the initial response of dispersed cells to activin concentration is unexpectedly simple, showing neither the thresholds of activin concentration nor the distinct domains of gene expression that characterize the later response. The eventual emergence of an ordered series of coherent differentiation steps requires the reaggregation of the induced cells, implying that secondary interactions occur. Furthermore, when cells induced at different doses of activin are mixed, the final response apparently represents a consensus, rather than a mosaic, of the mixed populations.


CONCLUSIONS
We conclude that communication among responding cells underlies much of the remarkable patterning influence of activin. Moreover, we suggest that these findings can inform thinking about how inducer gradients might act in other systems, shifting emphasis from the initial response of cells to inducer concentration toward the elaboration of complex pattern by secondary interactions.
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
P A
PA
Wilson
D A
DA
Melton
D000199:Actins / Q000096:biosynthesis; D028341:Activins; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D001755:Blastocyst / Q000187:drug effects; D002449:Cell Aggregation; D002450:Cell Communication; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004475:Ectoderm / Q000187:drug effects; D047108:Embryonic Development; D004627:Embryonic Induction; D005326:Fetal Proteins / Q000096:biosynthesis; D005786:Gene Expression Regulation; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D007265:Inhibins / Q000494:pharmacology / Q000502:physiology*; D008648:Mesoderm / Q000648:ultrastructure*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009024:Morphogenesis; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D014982:Xenopus laevis / Q000196:embryology*; D000098908:Brachyury Protein
D000199:Actins; D028341:Activins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D007265:Inhibins; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein