1.6.3 Hematopoisesis in zebrafish
Within the past two decades, the zebrafish (Danio rerio) has become an excellent model to study the development of hematopoietic stem cells (HSCs). The genes and molecular signaling pathways controlling hematopoiesis are highly conserved between fish and mammals. Both share all major blood cell types that are generated from common lineages of hematopoietic stem cells [13]. This is an important advantage over invertebrate models that lack the complex hematopoietic and adaptive immune system of vertebrates.
Hematopoiesis in all the vertebrates including zebrafish occurs in two waves i.e, primitive and definitive. Site of each event is different.
Fig5. Spatial and temporal representation of hematopoiesis in …show more content…
trafficking throughout life is believed to be central to hematopoiesis under homeostasis.
Two-way trafficking occurs within the body: 1- homing of HSCs to bone marrow and their lodging to the specific sites or micro environment known as niches. 2- Egress of HSCs from bone marrow into bloodstream.
HSC migration during the early embryonic development
The zebrafish AGM HSCs migrate to the caudal hematopoietic tissue (CHT) that performs the functions of both fetal liver and placenta in mammals, providing transient niche to support definitive HSC expansion and differentiation. Later these HSCs continue their migration toward the kidney serving, like the mammalian BM, as the definitive site of hematopoiesis for the adult life.
Definitive hematopoietic stem cell pools emerge from intra- (AGM) and extra- (yolk sac and placenta) embryonic hematopoietic sites. When the circulation is established and functional post 24hpf , HSCs start their migratory journey and colonize the placenta, followed by the fetal liver that becomes the major hematopoietic organ until the bone marrow/kidney is colonized by HSCs. The adhesion molecule VE-cadherin expression has been suggested to participate in HSC/progenitor migration but there is no functional data about the molecular mediators of HSC migration in the embryo. The colonization of the fetal liver and the bone marrow/kidney are dependent on β1 integrins and the CXCL12/CXCR4 …show more content…
HSC express high levels of α4β1 and also some α4β7, both which can mediate rolling on VCAM-1. Rolling interactions allow HSC to sample the chemokine CXCL12 presented in microdomains on the endothelial surface. CXCL12 is known to activate HSC through the G-protein coupled receptor CXCR4, leading to high affinity integrin-mediated arrest. Furthermore CXCL12 may translocate from the endothelial cells to the parenchyma, affecting the migration of HSCs throughout BM. CXCL12/CXCR4 axis crosstalks with other pathways that may enhance the migration of
Within the past two decades, the zebrafish (Danio rerio) has become an excellent model to study the development of hematopoietic stem cells (HSCs). The genes and molecular signaling pathways controlling hematopoiesis are highly conserved between fish and mammals. Both share all major blood cell types that are generated from common lineages of hematopoietic stem cells [13]. This is an important advantage over invertebrate models that lack the complex hematopoietic and adaptive immune system of vertebrates.
Hematopoiesis in all the vertebrates including zebrafish occurs in two waves i.e, primitive and definitive. Site of each event is different.
Fig5. Spatial and temporal representation of hematopoiesis in …show more content…
trafficking throughout life is believed to be central to hematopoiesis under homeostasis.
Two-way trafficking occurs within the body: 1- homing of HSCs to bone marrow and their lodging to the specific sites or micro environment known as niches. 2- Egress of HSCs from bone marrow into bloodstream.
HSC migration during the early embryonic development
The zebrafish AGM HSCs migrate to the caudal hematopoietic tissue (CHT) that performs the functions of both fetal liver and placenta in mammals, providing transient niche to support definitive HSC expansion and differentiation. Later these HSCs continue their migration toward the kidney serving, like the mammalian BM, as the definitive site of hematopoiesis for the adult life.
Definitive hematopoietic stem cell pools emerge from intra- (AGM) and extra- (yolk sac and placenta) embryonic hematopoietic sites. When the circulation is established and functional post 24hpf , HSCs start their migratory journey and colonize the placenta, followed by the fetal liver that becomes the major hematopoietic organ until the bone marrow/kidney is colonized by HSCs. The adhesion molecule VE-cadherin expression has been suggested to participate in HSC/progenitor migration but there is no functional data about the molecular mediators of HSC migration in the embryo. The colonization of the fetal liver and the bone marrow/kidney are dependent on β1 integrins and the CXCL12/CXCR4 …show more content…
HSC express high levels of α4β1 and also some α4β7, both which can mediate rolling on VCAM-1. Rolling interactions allow HSC to sample the chemokine CXCL12 presented in microdomains on the endothelial surface. CXCL12 is known to activate HSC through the G-protein coupled receptor CXCR4, leading to high affinity integrin-mediated arrest. Furthermore CXCL12 may translocate from the endothelial cells to the parenchyma, affecting the migration of HSCs throughout BM. CXCL12/CXCR4 axis crosstalks with other pathways that may enhance the migration of