Development of Megakaryocytes

Megakaryocytes (MKs) comprise a rare population of bone marrow cells, responsible for the production of platelets. MKs are derived from hematopoietic stem cells and share some common progenitors with the erythroid lineage. Through a partially elucidated interplay of transcription and growth factors, cells committed to the MK lineage are formed. Diploid MKs undergo multiple rounds of endomitosis, including aborted mitosis and cytokinesis. The mediators of endomitosis include cyclins, proteins involved in mitosis and cytokinesis, and other yet unrecognized proteins. Several signaling pathways are activated during endomitosis but their precise role remains largely uncharacterized. Endomitosis leads to high states of ploidy, which are accompanied by a cytoplasmatic volume increase. During the final stages of the MK life cycle biogenesis of platelets occurs. The precise mechanism of this aspect remained controversial for many years, but the implementation of sophisticated imaging modalities has gradually elucidated the process of proplatelet formation. Several disorders have been described affecting MK and platelet physiology. For some of them, the molecular pathology has been elucidated. Translational research has led to the development of thrombopoietic agents that are engineered to overcome changes in platelet levels associated with these states. In this chapter, we discuss key aspects of MK physiology and structure and we explore the molecular pathways governing these fascinating cells under normal and some pathological conditions.