PROJECT SUMMARY
Disruption of developmental processes, often due to genetic mutation, can lead to structural birth defects
that have life-long consequences for affected individuals and their families. Identification of patient-
specific genetic changes, followed by mechanistic studies, can increase our understanding of how
developmental perturbations lead to defects and offer insight into potential future clinical interventions.
Our long-term goal is to identify molecular and cellular functions of patient-identified, disorder-associated
genes with unknown roles in embryonic development. Here, we focus on one such gene, Mannose-
Binding Lectin-Associated Serine Protease 1 (Masp1), mutations of which are associated with the
developmental disorder 3MC Syndrome. Our objective for this proposal is to identify the underlying
molecular functions of Masp1 in development. We have found that genetic perturbations of Masp1
expression (both overexpression and knockdown) in African Clawed Frog (Xenopus laevis) embryos
leads to complementary changes in dorsal anterior structures such as altered head size and cement
gland size and shape. Additionally, we found that Masp1 manipulation leads to altered gene expression
patterns suggestive of embryonic patterning defects that could disrupt ectodermal-derived tissues,
possibly through Masp1 intersection with the BMP signaling pathway. In this project, we will continue to
use Xenopus laevis as a model system to address our central hypothesis that Masp1 is involved in
ectoderm patterning through positive regulation of the BMP signaling gradient. First, we will perform
targeted genetic perturbations of Masp1 followed by phenotypic and gene expression analysis to identify
a role of Masp1 proteolytic cleavage in tissue patterning during gastrulation (Aim 1). Next, we will use
both targeted (in vivo luciferase reporter assay) and unbiased (co-immunoprecipitation followed by
LC/MS) approaches to identify Masp1 targets and determine how Masp1 regulates BMP signaling (Aim
2). Through this work, we will provide undergraduate and graduate students with meaningful research
experiences in the field of developmental biology. Upon completion of this study, we expect to determine
the mechanistic basis for Masp1 involvement in early development and identify a new player in regulation
of BMP morphogenic signaling with future implications for interventions of Masp1- and BMP-associated
developmental disorders.
