Proper control of multipotent/stem cell number and fate is essential for ensuing organ formation during development. beta 1-integrin, a subfamily of cell surface receptors, has a conserved role in maintenance of multipotent/stem cells, including renal progenitor cells, follicle stem cells, epidermal stem cells and neural stem cells. However, it remains unclear whether beta 1-integrin has a role in cardiac progenitor cell (CPC) development. Here we show that a mesodermal deletion of beta 1-integrin decreases Isl1+ cell number in the second pharyngeal arch (PA2), where CPCs undergo renewal and expansion. Mesp1 lineage-specific mosaicism revealed that beta 1-integrin-deleted Isl1+ cells do not proliferate in the PA2. Consistently, beta 1-integrin-deleted Isl1+ CPCs failed to expand in vitro, independent of PA2 cells. beta 1-integrin co-localized and physically associated with Numb, a crucial regulator of CPC renewal and expansion. Importantly, Numb/Numbl-deleted CPCs showed dramatic reduction in beta 1-integrin levels. These findings suggest that beta 1-integrin is a key mediator of the Numb pathway in CPC maintenance. (C) 2018 Elsevier Inc. All rights reserved.