Submitted June 28, 2006
Accepted October 3, 2006
The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis
Joanna M. Tober, Anne Koniski, Kathleen E McGrath, Radhika Vemishetti, Rachael Emerson, Karen KL de Mesy-Bentley, Richard Waugh, and James Palis*
University of Rochester Medical Center
* Corresponding author; email: james_palis{at}urmc.rochester.edu.
In the adult, platelets derive from unipotential megakaryocyte progenitors (Meg-CFC) that arise from bipotential erythroid/megakaryocyte progenitors (MEP). To better define the developmental origin of the megakaryocyte lineage, several aspects of megakaryopoiesis, including progenitors, maturing megakaryocytes and circulating platelets were examined in the murine embryo. We found that a majority of hemangioblast precursors during early gastrulation contain megakaryocyte potential. Combining progenitor assays with immunohistochemical analysis we identified two waves of MEP in the yolk sac associated with the primitive and definitive erythroid lineages. Primitive-MEP emerge at E7.25 along with megakaryocyte and primitive erythroid progenitors indicating that primitive hematopoiesis is bilineage in nature. Subsequently, definitive-MEP expand in the yolk sac with Meg-CFC and definitive erythroid progenitors. The first GP1b
-positive cells in the conceptus were identified in the yolk sac at E9.5, while large, highly reticulated platelets were detected in the embryonic bloodstream beginning at E10.5. At this time the number of megakaryocyte progenitors begins to decline in the yolk sac and expand in the fetal liver. We conclude that the megakaryocyte lineage initially originates from hemangioblast precursors during early gastrulation and is closely associated both with primitive and with definitive erythroid lineages in the yolk sac prior to the transition of hematopoiesis to intraembryonic sites.
