Dataset Information

CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis.

ABSTRACT: Development of the vertebrate blood lineages is complex, with multiple waves of hematopoietic precursors arising in different embryonic locations. Monopotent, or primitive, precursors first give rise to embryonic macrophages or erythrocytes. Multipotent, or definitive, precursors are subsequently generated to produce the adult hematopoietic lineages. In both the zebrafish and the mouse, the first definitive precursors are committed erythromyeloid progenitors (EMPs) that lack lymphoid differentiation potential. We have previously shown that zebrafish EMPs arise in the posterior blood island independently from hematopoietic stem cells (HSCs). In this report, we demonstrate that a fourth wave of hematopoietic precursors arises slightly later in the zebrafish aorta/gonad/mesonephros (AGM) equivalent. We have identified and prospectively isolated these cells by CD41 (itga2b) and cmyb expression. Unlike EMPs, CD41(+) AGM cells colonize the thymus to generate rag2(+) T lymphocyte precursors. Timelapse imaging and lineage tracing analyses demonstrate that AGM-derived precursors use a previously undescribed migration pathway along the pronephric tubules to initiate adult hematopoiesis in the developing kidney, the teleostean equivalent of mammalian bone marrow. Finally, we have analyzed the gene expression profiles of EMPs and AGM precursors to better understand the molecular cues that pattern the first definitive hematopoietic cells in the embryo. Together, these studies suggest that expression of CD41 and cmyb marks nascent HSCs in the zebrafish AGM, and provide the means to further dissect HSC generation and function in the early vertebrate embryo.

SUBMITTER: Bertrand JY

PROVIDER: S-EPMC2762343 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis.

Bertrand Julien Y JY Kim Albert D AD Teng Shutian S Traver David D

Development (Cambridge, England) 20080416 10

Development of the vertebrate blood lineages is complex, with multiple waves of hematopoietic precursors arising in different embryonic locations. Monopotent, or primitive, precursors first give rise to embryonic macrophages or erythrocytes. Multipotent, or definitive, precursors are subsequently generated to produce the adult hematopoietic lineages. In both the zebrafish and the mouse, the first definitive precursors are committed erythromyeloid progenitors (EMPs) that lack lymphoid differentia ...[more]

PMID: 18417622

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Project description:Injuries of the zebrafish kidney are rapidly repaired by a migratory response in two to three day-old embryos. While this migratory repair process re-establishes the integrity of the pronephric tubules independently of proliferation, fluid flow, intact cilia, or Wnt signaling, pronephros injuries before 36 hours post fertilization were repaired by a purse string-like mechanism that irreversibly occluded the pronephric tubules. Comparing the gene expression profiles between these two developmental stages and focusing on up-regulated zebrafish pronephros genes, we identified cxcl12a and myca as potential candidates orchestrating the migratory repair process. Zebrafish lines with either cxcl12a or cxcr4b mutations displayed striking repair abnormalities, confirming the requirement for cxc12a/cxcr4b signaling to override the ongoing collective cell migration and repair the pronephros injury. However, in contrast to the collective cell migration of the posterior lateral line primordium, cxc12a/cxcr4b signaling was dispensable for normal pronephros development. Zebrafish myca, the pronephros-specific homologue of human MYC, was also increased in cells participating in the repair response. The defective repair response caused by knockdown of myca resembled the abnormalities observed in cxcx12a/cxcr4b-deficient zebrafish, and was partially rescued by cxcr4b mRNA, suggesting that myca acts in part through up-regulating cxcr4b expression during the migration-based repair process. Kidney-specific knockout of Cxcl12 and Myc suppressed mitochondrial functions, reduced retinoic acid receptor signaling, and delayed the recovery after ischemic/reperfusion injury in mice. Tretinoin, known to stimulate Cxcr4 expression and mitochondrial metabolism, accelerated renal recovery. Thus, the zebrafish pronephros injury mode provides a systematic approach to identify molecules involved in the immediate repair response after kidney injury, and to design strategies to ameliorate this severe complication of human disease.

Project description:Key Points During glomerular capillary formation, endothelial cells sprout from the dorsal aorta and surround the bilateral glomerular primordia. Blood flow maintains tubular structures of the capillaries surrounding the glomerular primordia. Blood flow also promotes glomerular incorporation of blood vessels by inducing glomerular remodeling. Visual Abstract Background The renal glomerulus is a tuft of capillaries in Bowman’s capsule and functions as a blood-filtration unit in the kidney. The unique glomerular capillary tuft structure is relatively conserved through vertebrate species. However, the morphogenetic mechanism governing glomerular capillary tuft formation remains elusive. Methods To clarify how glomerular capillaries develop, we analyzed glomerular capillary formation in the zebrafish pronephros by exploiting fluorescence-based bio-imaging technology. Results During glomerular capillary formation in the zebrafish pronephros, endothelial cells initially sprouted from the dorsal aorta and formed the capillaries surrounding the bilateral glomerular primordia in response to podocyte progenitor-derived vascular endothelial growth factor-A. After formation, blood flow immediately occurred in the glomerular primordia-associated capillaries, while in the absence of blood flow, they were transformed into sheet-like structures enveloping the glomerular primordia. Subsequently, blood flow induced formation of Bowman’s space at the lateral sides of the bilateral glomerular primordia. Concomitantly, podocyte progenitors enveloped their surrounding capillaries while moving toward and coalescing at the midline. These capillaries then underwent extensive expansion and remodeling to establish a functional glomerular capillary tuft. However, stopping blood flow inhibited the remodeling of bilateral glomerular primordia, which therefore remained unvascularized but covered by the vascular sheets. Conclusions We delineated the morphogenetic processes governing glomerular capillary tuft formation in the zebrafish pronephros and demonstrated crucial roles of blood flow in its formation. Blood flow maintains tubular structures of the capillaries surrounding the glomerular primordia and promotes glomerular incorporation of these vessels by inducing the remodeling of glomerular primordia.

Dataset Information

CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis.

Publications

CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis.

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