Tailbud progenitor cells contribute to multiple tissues of the lengthening post-gastrula vertebrate embryo. Recent evidence shows that these cells continue to make germ layer decisions after gastrulation, contrary to long-held dogma. Wnt signaling and the transcription factor Sox2 are known regulators of these cells, and we have found an unexpected interaction between these two pathways.
The tailbud is a conserved structure in vertebrate embryos, formed at the posterior-most end of the body axis after gastrulation completes. Multiple progenitor cell pools are maintained in the tailbud, and these cells are continuously specified to different germ layer fates. In zebrafish the posterior-most progenitors make an ectoderm/mesoderm fate decision, primarily contributing to the neural tube or somites respectively. Wnt signaling and the transcription factor Sox2 are potent regulators of this fate decision. Undifferentiated progenitors express sox2 and reside in a region of active Wnt signaling. Cell fate is specified when a cell receives only one of the two signals. Sox2 is considered to have a pro-neural function in this context while Wnt specifies a mesodermal fate. Both signals can antagonize the activity of the other, likely serving to lock in a fate decision when the balance tips to one side within a cell. We use transgenic zebrafish that allow inducible overexpression of sox2 or manipulation of Wnt signaling to understand the role of these signals in tailbud progenitors.
We found an unexpected role for Sox2 in regulating the behavior of mesoderm-fated cells: Sox2 prevents the maturation program of these cells from progressing. A further surprising result is that Sox2 can respecify some mesoderm-fated cells to a neural fate. Precise regulation of Sox2 and Wnt levels is crucial both for maintenance of tailbud progenitors and for proper maturation of mesoderm-fated cells.