Obiettivo
During my PhD I concentrated on the transcriptional regulation of growth control and terminal differentiation in megakaryocytes leading to platelet release. All mature blood cells including platelets have a limited life-span and need to be constantly replaced during life.
As haemopoietic stem cells (HSCs) are the foundation for this life-long production, I became interested in the specification of the haemopoietic system from HSCs during ontogeny. In mammals the first adult-type HSCs arise in the Aorta-Gona d-Mesonephros (AGM) region at E10.5 of embryonic development. With the onset of circulation, these cells are believed to travel and seed other haemopoietic organs (fetal liver and bone marrow) later in development.
Once settled in the bone marrow, HSCs produce all mature blood cells during adult life. However, to date the path of migration of HSCs from the AGM to bone marrow or other haemopoietic sites has not been shown. Experiments outlined in this proposal will attempt to answer this question by generating compound mutant animals from three transgenic mouse strains.
HSCs will be specifically labelled with GFP at the time of their generation in the AGM region. If the hypothesis is correct, labelled GFP+ cells should migrate to the fetal liver and adult bon e marrow and give rise to other haemopoietic cells.
This would prove for the first time that AGM HSCs are able to migrate and serve as a source for mature blood cells throughout adult life. As the host institute has a long-standing interest and expertise i n the field of HSC biology it will provide excellent training and allow me to become an independent researcher in this field.
Campo scientifico
Parole chiave
Invito a presentare proposte
FP6-2005-MOBILITY-5
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