Poster Sessions

DEV-4

Sema Rosinbum

S. Rosinbum, T. Thomas, M. Moos

A Xenopus Homolog of SPC7 Is Essential to Eye Development

Subtilisin-like Proprotein Convertase 7 (SPC7) is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenic protein (BMP) family of signaling molecules. We demonstrated that XSPC7 was localized strongly to the eye and neural plate in Xenopus embryos. Since no prior functional information has been reported for SPC7, we therefore investigated the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6 using gain- and loss-of-function experiments. Consistent with its presumed role to activate a growth factor such as a BMP, overexpression of XSPC7 was without effect. In contrast, injection of an antisense- MO into a single blastomere at the 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation. In parallel with loss of the eye and mesencephalon by XSPC7 knockdown, expression of early (Sox2, Rx2, Otx2, and Pax6) and late (β-Crystallin and Opsin) eye markers, and of BMP target genes such as Tbx2 and Tbx3 was suppressed or eliminated. Moreover, whole mount immunostaining for Smad1/5/8 phosphorylation indicated decreased BMP signaling in the morpholino-injected embryos. Taken together, these findings suggest a critical role for XSPC7 in patterning of the Xenopus eye and central nerve system, perhaps, at least in part, due to activation of one or more BMPs.