Universidade do Algarve | 12h30 | Auditorium 1.8.1
Title: “From development to disease: towards understanding the onset of congenital muscular dystrophy ”
Abstract: Congenital muscular dystrophies (CMDs) are a group of diseases causing muscle weakness at birth. They affect ~1 child per 100.000 births. Most CMDs are due to mutations in genes involved in the link between the cytoskeleton of muscle fibres and their surrounding extracellular matrix. Currently, there is no cure for CMDs. MDC1A, the most common CMD, is due to a mutation in the LAMA2 gene which encodes the laminin α2 chain of laminin 211. Laminin 211 is the major laminin isoform in the basement membrane surrounding mature muscle fibres and its is thought to progressively damage the fibres, leading to muscle wasting.
We have recently used the dyW mouse model for MDC1A to trace the onset of the disease during development. We found that the disease starts as myogenesis defect during fetal stages without any signs of muscle wasting. More specifically, this defect involves a precocious reduction in the number of muscle stem cells (MuSCs) and a consequent failure in muscle growth in dyW fetuses, which persists postnatally. Our study marks a paradigm shift in the understanding of MDC1A pathogenesis because rather than putting deteriorating muscle fibre health as a first step in the disease, our data from a mouse model demonstrate that the primary defect arises because of impaired fetal myogenesis. Possible ways to build on this knowledge to develop therapeutic strategies addressing this primary defect will be discussed.
Short Bio: Solveig Thorsteinsdottir works on Developmental Biology and her research interests center on how cells in amniote embryos (chick and mouse) organize to form the musculoskeletal system and how the extracellular matrix produced by cells helps orchestrate this organizational process.
Part of the mesoderm of all vertebrate embryos segments into somites, transient balls of cells which contain most of the precursors of the axial musculoskeletal system. This system is common to and characterizes all vertebrates, and its functional modification over evolutionary time allowed the conquest of land.
Her research team ask questions such as: How do these apparently homogenous balls of cells give rise to a functional system composed of vertebrae, tendons, blood vessels and skeletal muscle, the latter which is innervated at precisely the appropriate time? How do specific mutations affect their developmental programme and lead to disease, such as the muscular dystrophies or developmental defects in the vertebral column? How were the development of somites and their derivatives modified to produce a muscle pattern able to sustain the vertebral column on land?