THESIS
2016
xiii, 61 pages : illustrations (some color) ; 30 cm
Abstract
In vertebrates, myeloid cells can be derived from multiple waves of myelopoiesis: the
primitive or embryonic wave originates from hematopoietic progenitors during the early
development stages and gives rise to myeloid cells transiently; whereas the definitive or adult
wave of myelopoiesis initiates from Hematopoietic Stem Cells (HSCs) at later stages and
produces myeloid cell lineages throughout the life span of organisms. In the past decades,
numerous studies have been performed to explore the development of adult myelopoiesis
derived myeloid cells. However, the genetic network governing embryonic myelopoiesis
remains poorly defined. In this thesis, we present an in vivo study to delineate the role of
Cebpα during zebrafish embryonic myelopoiesis. Via ENU forward genetic screen...[
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In vertebrates, myeloid cells can be derived from multiple waves of myelopoiesis: the
primitive or embryonic wave originates from hematopoietic progenitors during the early
development stages and gives rise to myeloid cells transiently; whereas the definitive or adult
wave of myelopoiesis initiates from Hematopoietic Stem Cells (HSCs) at later stages and
produces myeloid cell lineages throughout the life span of organisms. In the past decades,
numerous studies have been performed to explore the development of adult myelopoiesis
derived myeloid cells. However, the genetic network governing embryonic myelopoiesis
remains poorly defined. In this thesis, we present an in vivo study to delineate the role of
Cebpα during zebrafish embryonic myelopoiesis. Via ENU forward genetic screening, We
identified a cebpα
hkz7 mutant zebrafish, in which the mutation results in a truncated
dysfunction Cebpα protein. Phenotype characterization shows that embryonic myelopoiesis is
initiated properly but fails to generate mature macrophages and neutrophils in cebpα-deficiency zebrafish embryos. Further cell cycle and cell death analysis indicates that the
absence of macrophages and neutrophils in the mutants is attributed to the cell cycle arrest of
embryonic myeloid progenitors in S phase, thereby blocking their maintenance and
subsequent differentiation. Besides, We find that Cebpα can cooperate with Runx1 to regulate
embryonic neutrophil maintenance. To sum up, Our findings reveal a new role of Cebpα in
embryonic myelopoiesis.
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