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PMID:10654605

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Citation

Lee, CS, Buttitta, LA, May, NR, Kispert, A and Fan, CM (2000) SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Development 127:109-18

Abstract

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.

Links

PubMed

Keywords

3T3 Cells; Animals; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins/physiology; COS Cells; Carrier Proteins; Eye Proteins/genetics; Eye Proteins/metabolism; Glycoproteins; Hedgehog Proteins; Membrane Proteins; Mesoderm/physiology; Mice; Notochord; Proteins/genetics; Proteins/metabolism; Proteins/physiology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Trans-Activators; Up-Regulation; Wnt Proteins; Wnt1 Protein; Wnt4 Protein; Zebrafish Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WNT4

involved_in

GO:0061184: positive regulation of dermatome development

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P56705

P

Seeded From UniProt

complete

MOUSE:SFRP2

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SFRP3

involved_in

GO:0014033: neural crest cell differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP3

involved_in

GO:0061053: somite development

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP1

involved_in

GO:0001756: somitogenesis

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT1

involved_in

GO:0061184: positive regulation of dermatome development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT4

involved_in

GO:0061184: positive regulation of dermatome development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT3A

involved_in

GO:0061184: positive regulation of dermatome development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP2

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SFRP2

involved_in

GO:0030178: negative regulation of Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP2

involved_in

GO:0061056: sclerotome development

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP2

involved_in

GO:0061185: negative regulation of dermatome development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SHH

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SHH

involved_in

GO:0061189: positive regulation of sclerotome development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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