Role of Hey2 in heart progenitors and cardiac regeneration
Description: Heart disease remains the major cause of death in North American adults. Lost heart muscle is not replaced following events such as heart attacks. The heart compensates for this to maintain sufficient pump function in a way that ultimately leads to heart failure. Further, congenital heart defects occur in close to 1% of live births, and can have a severe impact on the health and mortality of children. Despite many years of research, little is known about the stem cells that go on to form the different types of cells found in the heart. These cells are called cardiac progenitors. As they are the "building blocks" of the heart, cardiac progenitors are an ideal vehicle to fix the damaged heart. We study this in zebrafish embryos, which allow live and direct visualization of all stages of heart development. Further, the adult zebrafish heart can fully regenerate, a process we seek to understand in order to allow human cardiac repair. In this project, we aim to uncover how a gene called Hey2 regulates the way in which cardiac progenitors make the components of the heart. We have found that Hey2 acts as a master "brake" on stem cells, with cardiac progenitors dividing more and adding more cells to the heart in the absence of Hey2 function. Further, during adult heart regeneration, Hey2 expression is turned off immediately after injury, suggesting that again it is a master brake that must be relieved to allow regeneration. Learning how Hey2 regulates embryonic development and adult heart regeneration are critical first steps towards finding means to drive repair of the human heart. This knowledge will be used to devise therapies based on activating regenerative pathways to heal the damaged heart, and using zebrafish embryos to screen for potential drugs to alleviate the burden of congenital heart defects. Discovering how zebrafish cardiac progenitors are made and develop will therefore drive future efforts to repair what is at present irreparable heart disease.
Amount: CA$769,200
Funding type: research
Funder scheme: Project Grant
Start date: 2018-04-01
End date: 2023-03-31
Investigator: Ian Scott
Institution: Hospital for Sick Children (Toronto)
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 3
Funder award ID: 156318_1
OpenAlex ID: G1364555086