Scube2 expression extends beyond the central nervous system during mouse development

Abstract

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.

Scube3 Is Expressed in Multiple Tissues during Development but Is Dispensable for Embryonic Survival in the Mouse

“…Whilst Scube2 expression does extend beyond the myotome in both fish and mouse embryos [4], [16], expression in the developing mouse tooth is negligible, only being present above background levels from around E16.5 within the mesenchyme (Fig. 7A–C).…”

“…Although widely expressed in the mouse embryo [1], [2], [3], [13], [16], [17] there is currently only limited data relating to the function of Scube genes during mouse development. In mice with targeted disruption in Scube1 , there is normal limb and skeletal development but acrania, associated with severe disruption of the flat bones within the cranial vault and exencephaly, possibly secondary to a role in antagonizing BMP signaling [9].…”

Transcriptome Comparison of Human Neurons Generated Using Induced Pluripotent Stem Cells Derived from Dental Pulp and Skin Fibroblasts

“…SLITRK2 codes for an integral membrane protein that shares homology with neurotrophin receptors; it has been implicated in a small subset of patients with BD and ASD [34], [35]. SCUBE2 is expressed in the hindbrain and forms a complex with Sonic hedgehog and its receptor PTC1 to activate SHH-signaling [36], [37].…”

SCUBE3 (Signal Peptide-CUB-EGF Domain-containing Protein 3) Modulates Fibroblast Growth Factor Signaling during Fast Muscle Development

“…SCUBE3 [signal peptide-CUB (complement protein C1r/ C1s, Uegf, and Bmp1)-EGF-like domain-containing protein 3] belongs to the secreted and membrane-associated SCUBE family composed of three members evolutionarily conserved from zebrafish to humans (1)(2)(3)(4)(5)(6)(7)(8). Proteins encoded by these genes are organized in a modular fashion and share at least five protein domains: 1) an NH 2 -terminal signal peptide sequence, 2) nine copies of EGF-like repeats, 3) a spacer region, 4) three cysteinerich motifs, and 5) one CUB domain at the COOH terminus.…”

“…Proteins encoded by these genes are organized in a modular fashion and share at least five protein domains: 1) an NH 2 -terminal signal peptide sequence, 2) nine copies of EGF-like repeats, 3) a spacer region, 4) three cysteinerich motifs, and 5) one CUB domain at the COOH terminus. Scube gene expression is overlapping and/or complementary to each other in vertebrate embryos, with transcripts predominating in the somites, central nervous system, and notochord early during development (2,3,7). Thus, these Scube genes may have critical functions during development in these tissue sites, where delicate signaling of morphogens or growth factors are transmitted by cell surface receptors including receptor serine/ threonine kinases and receptor tyrosine kinases (RTKs) 2 (9,10).…”