Altered Masp1 Levels Affect Gene Expression Patterns During Gastrulation
Additional Funding Sources
This project is supported by a 2021-2022 STEM Undergraduate Research Grant from the Higher Education Research Council, the NSF Idaho EPSCoR Program, and the National Science Foundation under Award No. OIA-1757324. Additional support was received from ISU Start Up Funds HR.
Abstract
Mannan-binding lectin associated protease 1 (MASP1) is a component of the lectin complement pathway of the innate immune system. Previous research identified mutations in Masp1/3, the gene encoding MASP1, in patients with 3MC Syndrome, a developmental disorder that causes craniofacial malformations, and cognitive impairment. This suggests that MASP1 is important during early development Here, we are using African Clawed Frog (Xenopus laevis) embryos to better understand the role of Masp1 in development. Embryos were injected with either masp1 RNA (overexpression) or masp1 morpholino (knockdown) and allowed to further develop. Multiple phenotypes were identified including defects in gastrulation and cement gland development. In situ hybridization was then used to visualize the expression patterns of genes important for gastrulation and cement gland development and to identify the impact of altered masp1 levels. Masp1 overexpression showed an increase in the expression of the genes bmp4, chordin, and otx2 while masp1 knockdown results in increased noggin expression. These findings demonstrate that Masp1 impacts the expression of genes during gastrulation, potentially having consequences on later development. Continuing studies will determine how these gene expression changes occur over developmental time. Our results will shed light on how MASP1/3 mutation could lead to 3MC Syndrome.
Altered Masp1 Levels Affect Gene Expression Patterns During Gastrulation
Mannan-binding lectin associated protease 1 (MASP1) is a component of the lectin complement pathway of the innate immune system. Previous research identified mutations in Masp1/3, the gene encoding MASP1, in patients with 3MC Syndrome, a developmental disorder that causes craniofacial malformations, and cognitive impairment. This suggests that MASP1 is important during early development Here, we are using African Clawed Frog (Xenopus laevis) embryos to better understand the role of Masp1 in development. Embryos were injected with either masp1 RNA (overexpression) or masp1 morpholino (knockdown) and allowed to further develop. Multiple phenotypes were identified including defects in gastrulation and cement gland development. In situ hybridization was then used to visualize the expression patterns of genes important for gastrulation and cement gland development and to identify the impact of altered masp1 levels. Masp1 overexpression showed an increase in the expression of the genes bmp4, chordin, and otx2 while masp1 knockdown results in increased noggin expression. These findings demonstrate that Masp1 impacts the expression of genes during gastrulation, potentially having consequences on later development. Continuing studies will determine how these gene expression changes occur over developmental time. Our results will shed light on how MASP1/3 mutation could lead to 3MC Syndrome.