All conscious movement uses skeletal muscles, which are organized into a complex musculature that moves skeletal joints. To function, these muscles need to be positioned correctly during development and generate intricate contractile machinery. Our lab investigates how the musculature forms using zebrafish embryos.
1) What cues control muscle precursor cell movements?
In all vertebrate species, a subset of muscle progenitors migrate to new locations in the embryo. These muscle precursors move in loosely associated streams, similar to the movement of metastatic tumors. In zebrafish, all of the precursor streams begin close to one another, but clump into separate streams that generate different muscles. We are using zebrafish embryos to identify the intrinsic and extrinsic cues that control these cell movements. These cues will teach us about muscle formation and potentially about cancer, since the cell movements and core genes known to drive muscle precursor migration are also known to promote tumor metastasis.
2) How do muscle fibers produce contractile structures?
When muscle precursors begin to form muscle fibers they generate repeated arrays of Actin and Myosin filaments in units called sarcomeres. These Actin and Myosin filaments slide across one another to contract the muscle fiber or can release from one another to allow muscle extension. We have identified genes essential for sarcomere formation, that we hypothesize to function by controlling Actin-Myosin interactions. We are investigating how these genes influence Actin-Myosin interactions and how variants in sarcomeric protein can impact human health.