Event Title

The role of fli1a and fli1b during zebrafish hematopoietic stem cell and vascular development

Date

1-4-2017 12:00 AM

Major

Biology

Department

Genetics, Development, and Cell Biology

College

College of Liberal Arts and Sciences

Project Advisor

Jeffrey Essner

Project Advisor's Department

Genetics, Development and Cell Biology

Description

We have isolated Tol2 gene trap insertional and indel mutations from CRISPR/Cas9 targeting in the fli1a and fli1b genes. While all mutants are homozygous viable, defects were observed in hematopoietic stem cell development. A major hallmark of vertebrate hematopoiesis is a temporally and spatially switching from one anatomical niche to another. In zebrafish, hematopoietic stem cells (HSCs) are born in and near the ventral wall of dorsal aorta (VDA), and subsequently migrate to the caudal hematopoietic tissue (CHT). The CHT is thought to be an intermediate hematopoietic site where the HSC undergo further proliferation and differentiation. In both fli1a and fli1b mutant embryos, the HSCs originated properly in VDA, but subsequent migration to the CHT and onward colonization to either thymus or kidney was severely impaired. Our results suggest that the fli1a and fli1b transcription factors play a crucial role in the regulation of early hematopoietic development. Fli1a/fli1b double mutants have severe defects in vascular development. At 48 hpf, double mutant fli1 embryos lack circulation and have accumulation of HSCs in the VDA region and fail to transition into the vasculature and to colonize to the CHT. Taken together, fli1a and fli1b mutants reveal distinct gene dosage requirements for fli1 during HSC and vascular development.

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Apr 1st, 12:00 AM

The role of fli1a and fli1b during zebrafish hematopoietic stem cell and vascular development

We have isolated Tol2 gene trap insertional and indel mutations from CRISPR/Cas9 targeting in the fli1a and fli1b genes. While all mutants are homozygous viable, defects were observed in hematopoietic stem cell development. A major hallmark of vertebrate hematopoiesis is a temporally and spatially switching from one anatomical niche to another. In zebrafish, hematopoietic stem cells (HSCs) are born in and near the ventral wall of dorsal aorta (VDA), and subsequently migrate to the caudal hematopoietic tissue (CHT). The CHT is thought to be an intermediate hematopoietic site where the HSC undergo further proliferation and differentiation. In both fli1a and fli1b mutant embryos, the HSCs originated properly in VDA, but subsequent migration to the CHT and onward colonization to either thymus or kidney was severely impaired. Our results suggest that the fli1a and fli1b transcription factors play a crucial role in the regulation of early hematopoietic development. Fli1a/fli1b double mutants have severe defects in vascular development. At 48 hpf, double mutant fli1 embryos lack circulation and have accumulation of HSCs in the VDA region and fail to transition into the vasculature and to colonize to the CHT. Taken together, fli1a and fli1b mutants reveal distinct gene dosage requirements for fli1 during HSC and vascular development.