Division of Cellular and Gene Therapies, Center for Biologics, Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland, United States of America.
PLoS One. 2012;7(6):e39380. doi: 10.1371/journal.pone.0039380. Epub 2012 Jun 28.
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 morphogenetic protein (BMP) family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously.
METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that Xenopus SPC7 (SPC7) was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain- and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO) into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6) and late eye-specific markers (β-Crystallin and Opsin), and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7-perhaps, at least in part, due to activation of one or more BMPs-in early patterning of the anterior neural plate and its derivatives.
CONCLUSION/SIGNIFICANCE: SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded.
枯草溶菌素样前蛋白转化酶 7（SPC7）是枯草杆菌蛋白酶/柯萨奇蛋白酶家族的前蛋白转化酶成员。它能裂解许多前蛋白，释放其活性蛋白，包括骨形态发生蛋白（BMP）家族的信号分子成员。其他 SPC 在胚胎发育过程中是必需的，但之前没有关于 SPC7 的相应数据报道。
方法/主要发现：我们证明，爪蟾 SPC7（SPC7）主要在脑和眼发育过程中表达，最初在整个神经板中表达，然后随着发育的进行，更特异于晶状体和视网膜原基表达。由于之前没有关于 SPC7 的功能信息报道，我们利用获得和丧失功能实验来研究它是否也能像 Furin、SPC4 和 SPC6 一样传递模式或组织特化信息的可能性。SPC7 的过表达没有效果。相反，在 2-或 4-细胞期将 SPC7 反义 MO 注射到单个卵裂球中，会导致头部结构明显破坏；眼球缺失明显。双侧注射完全抑制了头部和眼部的形成。SPC7 敲低抑制眼部和脑部发育的同时，早期前脑神经标记物（Sox2、Otx2、Rx2 和 Pax6）和晚期眼部特异性标记物（β-晶状体蛋白和视蛋白）的表达，以及 BMP 靶基因（如 Tbx2 和 Tbx3）的表达，均减少或消除。综上所述，这些发现表明 SPC7 可能在一定程度上通过激活一种或多种 BMPs 在神经板前部及其衍生物的早期模式形成中发挥关键作用。
结论/意义：SPC7 是眼睛和大脑正常发育所必需的，可能是通过加工 BMP 来实现的，但不能排除其他潜在的底物。
