%0 Journal Article
%T Novel Insights into the Genetic Controls of Primitive and Definitive Hematopoiesis from Zebrafish Models
%A Raman Sood
%A Paul Liu
%J Advances in Hematology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/830703
%X Hematopoiesis is a dynamic process where initiation and maintenance of hematopoietic stem cells, as well as their differentiation into erythroid, myeloid and lymphoid lineages, are tightly regulated by a network of transcription factors. Understanding the genetic controls of hematopoiesis is crucial as perturbations in hematopoiesis lead to diseases such as anemia, thrombocytopenia, or cancers, including leukemias and lymphomas. Animal models, particularly conventional and conditional knockout mice, have played major roles in our understanding of the genetic controls of hematopoiesis. However, knockout mice for most of the hematopoietic transcription factors are embryonic lethal, thus precluding the analysis of their roles during the transition from embryonic to adult hematopoiesis. Zebrafish are an ideal model organism to determine the function of a gene during embryonic-to-adult transition of hematopoiesis since bloodless zebrafish embryos can develop normally into early larval stage by obtaining oxygen through diffusion. In this review, we discuss the current status of the ontogeny and regulation of hematopoiesis in zebrafish. By providing specific examples of zebrafish morphants and mutants, we have highlighted the contributions of the zebrafish model to our overall understanding of the roles of transcription factors in regulation of primitive and definitive hematopoiesis. 1. Zebrafish as a Model for Hematopoiesis Recently, zebrafish have emerged as a powerful vertebrate model system due to their external fertilization, optically clear embryos, rapid development, availability of tools for manipulations of gene expression during development, and the ability to generate genetic mutants by random (insertional and chemical) and targeted mutagenesis [1¨C3]. Microinjections of antisense morpholinos, which cause transient knockdown of gene activity, and mRNA allows for analysis of the effects of loss and gain of function of specific genes during development [4]. Whole-mount in situ hybridization (WISH) is a powerful technique to analyze the spatiotemporal expression of genes, and placing genes in regulatory cascades by analysis of genetic mutants and/or embryos injected with morpholinos (commonly termed as morphants) [5, 6]. Specifically for hematopoiesis, zebrafish blood contains cells of all hematopoietic lineages [7¨C11] and orthologs of most transcription factors involved in mammalian hematopoiesis have been identified indicating evolutionarily conserved pathways of regulation [12¨C15]. Initial validation of the use of zebrafish for hematopoiesis research
%U http://www.hindawi.com/journals/ah/2012/830703/