PMID- 10654605 OWN - NLM STAT- MEDLINE DCOM- 20000303 LR - 20220224 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 127 IP - 1 DP - 2000 Jan TI - SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. PG - 109-18 AB - Dorsoventral polarity of the somitic mesoderm is established by competitive signals originating from adjacent tissues. The ventrally located notochord provides the ventralizing signals to specify the sclerotome, while the dorsally located surface ectoderm and dorsal neural tube provide the dorsalizing signals to specify the dermomyotome. Noggin and SHH-N have been implicated as the ventralizing signals produced by the notochord. Members of the WNT family of proteins, on the other hand, have been implicated as the dorsalizing signals derived from the ectoderm and dorsal neural tube. When presomitic explants are confronted with cells secreting SHH-N and WNT1 simultaneously, 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 its own receptor Ptc1, but also by upregulating Sfrp2 (Secreted frizzled-related protein 2), which encodes a potential WNT antagonist. Among the four known Sfrps, Sfrp2 is the only member expressed in the sclerotome and upregulated by SHH-N recombinant protein. We further show that SFRP2-expressing cells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but not that of WNT3a. Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm. FAU - Lee, C S AU - Lee CS AD - Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210, USA. FAU - Buttitta, L A AU - Buttitta LA FAU - May, N R AU - May NR FAU - Kispert, A AU - Kispert A FAU - Fan, C M AU - Fan CM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Bmp4 protein, mouse) RN - 0 (Bone Morphogenetic Protein 4) RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Carrier Proteins) RN - 0 (Eye Proteins) RN - 0 (Glycoproteins) RN - 0 (Hedgehog Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Sfrp2 protein, mouse) RN - 0 (Trans-Activators) RN - 0 (WD repeat containing planar cell polarity effector) RN - 0 (Wnt Proteins) RN - 0 (Wnt1 Protein) RN - 0 (Wnt1 protein, mouse) RN - 0 (Wnt4 Protein) RN - 0 (Wnt4 protein, mouse) RN - 0 (Zebrafish Proteins) RN - 0 (bmp4 protein, zebrafish) RN - 148294-77-3 (noggin protein) SB - IM MH - 3T3 Cells MH - Animals MH - Bone Morphogenetic Protein 4 MH - Bone Morphogenetic Proteins/physiology MH - COS Cells MH - Carrier Proteins MH - Eye Proteins/genetics/*metabolism MH - *Glycoproteins MH - Hedgehog Proteins MH - Intracellular Signaling Peptides and Proteins MH - *Membrane Proteins MH - Mesoderm/*physiology MH - Mice MH - Notochord MH - Proteins/genetics/*metabolism/physiology MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Recombinant Fusion Proteins/genetics/metabolism MH - *Trans-Activators MH - Up-Regulation MH - Wnt Proteins MH - Wnt1 Protein MH - Wnt4 Protein MH - *Zebrafish Proteins EDAT- 2000/02/02 09:00 MHDA- 2000/03/11 09:00 CRDT- 2000/02/02 09:00 PHST- 2000/02/02 09:00 [pubmed] PHST- 2000/03/11 09:00 [medline] PHST- 2000/02/02 09:00 [entrez] AID - 10.1242/dev.127.1.109 [doi] PST - ppublish SO - Development. 2000 Jan;127(1):109-18. doi: 10.1242/dev.127.1.109.