SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm

Dorsoventral polarity of the semitic mesoderm is established by competitive signals originating from adjacent tissues. The ventrally located notochord provides the ventralizing signals to specify the sclerotome, while the dor sally located surface ectoderm and dorsal neural tube provide the dorsalizi ng signals to specify the dermomyotome. Noggin and SHH-N have been implicat ed as the ventralizing signals produced by the notochord, Members of the WN T family of proteins, on the other hand, have been implicated as the dorsal izing signals derived from the ectoderm and dorsal neural tube. When presom itic explants are confronted with cells secreting SHH-N and WNT1 simultaneo usly, competition to specify the sclerotome and dermomyotome domains within the naive mesoderm can be observed. Here, using these explant cultures, we provide evidence that SHH-N competes with WNT1, not only by upregulating i ts own receptor Ptc1, but also by upregulating Sfrp2 (Secreted frizzled-rel ated protein 2), which encodes a potential WNT antagonist. Among the four k nown Sfrps, Sfrp2 is the only member expressed in the sclerotome and upregu lated by SHH-N recombinant protein. We further show that SFRP2-expressing c ells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but no t that of WNT3a. Together, our results support the model that SHH-N at leas t in part employs SFRP2 to reduce WNT1/4 activity in the semitic mesoderm.