Abstract
The vertebrate Scube family consists of three independent members Scube1-3; which encode secreted cell surface-associated membrane glycoproteins that share a domain organization of at least five recognizable motifs and the ability to both homo- and heterodimerize. There is recent biochemical evidence to suggest that Scube2 is directly involved in Hedgehog signaling, acting co-operatively with Dispatched to mediate the release in soluble form of cholesterol and palmitate-modified Hedgehog ligand during long-range activity. Indeed, in the zebrafish myotome, all three Scube proteins can subtly promote Hedgehog signal transduction in a non-cell autonomous manner. In order to further investigate the role of Scube genes during development, we have generated mice with targeted inactivation of Scube3. Despite a dynamic developmental expression pattern, with transcripts present in neuroectoderm, endoderm and endochondral tissues, particularly within the craniofacial region; an absence of Scube3 function results in no overt embryonic phenotype in the mouse. Mutant mice are born at expected Mendelian ratios, are both viable and fertile, and seemingly retain normal Hedgehog signaling activity in craniofacial tissues. These findings suggest that in the mouse, Scube3 is dispensable for normal development; however, they do not exclude the possibility of a co-operative role for Scube3 with other Scube members during embryogenesis or a potential role in adult tissue homeostasis over the long-term.
Highlights
The Scube (Signal peptide CUB EGF-like domain-containing protein) family consists of three independent members evolutionarily conserved from zebrafish to humans [1,2,3,4,5,6]
Biochemical evidence from cultured cell assays has emerged to suggest that the mode-of-action underlying Scube2 function is to enhance the secretion and solubility of Sonic hedgehog (Shh), synergizing with Dispatched to facilitate the release of lipidmodified forms of this ligand during long-range signaling [10,11]
Scube3 expression in the developing craniofacial region We have previously demonstrated strong expression of Scube3 in neuroectoderm of the developing mouse embryo from E8.5, with transcripts localizing to other tissues during later development, including CNS, endoderm and endochondral condensations associated with the early skeleton [3]
Summary
The Scube (Signal peptide CUB EGF-like domain-containing protein) family consists of three independent members evolutionarily conserved from zebrafish to humans [1,2,3,4,5,6]. Mutations in Scube have been identified in the you mutant, characterized by abnormal somite morphology and reduced numbers of both muscle pioneer cells and slow twitch populations within the myotome. These defects are secondary to a loss of long-range Hedgehog signaling in this region, with Scube acting in a non-cell autonomous manner [5,7,8]. SCUBE3 can complex with TGFb1 through its carboxy and/or amino-terminal domain, significantly promoting TGFb1-induced transcriptional activation in HepG2 cells [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
