Scube2 expression extends beyond the central nervous system during mouse development

The Scube (Signal peptide CUB EGF-like domain-containing protein) family consists of three independent members evolutionarily conserved from zebrafish to humans. Scube2 transcripts have been identified primarily in forebrain and trunk neuroepithelium and the anterior hindbrain of the mouse embryo, becoming progressively localized to the dorsal forebrain, hindbrain and neural tube. Zebrafish You-class mutants lack a functional C-terminal domain within the Scube2 protein and present with altered myotomal morphology, curled tail and weak cyclopia. These defects are characteristic of disrupted Hedgehog signaling, which is consistent with the downregulation of Hedgehog targets such as Ptc1, MyoD and Eng observed in these mutants. Indeed, human SCUBE2 can form a complex with Sonic hedgehog and its receptor PTC1, acting to promote SHH-induced signaling. Here we have characterized Scube2 expression in detail within the developing mouse embryo using wholemount and section in situ hybridisation and demonstrate the presence of transcripts within a more extensive range than previously reported. In addition to neuroectoderm of the early embryo, expression was also found in the developing face, heart, vasculature and multiple regions of the endochondral skeleton. These findings suggest that Scube2 may play an important role during development of multiple regions in the embryo.