Hematopoietic and Vascular System Toxicity - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 70

Chapter 7

Hematopoietic and Vascular
System Toxicity

Alison M. Taylor and Leonard I. Zon
Stem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston
and Dana Farber Cancer Institute, Harvard Medical School

7.1 INTRODUCTION

Research in recent decades has demonstrated a high level of conservation of
hematopoietic and vascular development among all vertebrates, including zebrafish
(de Jong and Zon, 2005; Baldessari and Mione, 2008). Not only are regulatory
networks conserved, but work from our lab also demonstrates that the effect of
chemical compounds on zebrafish blood, stem cells, and vasculature can be extrap-
olated to mouse and other mammals (North et al., 2007). Furthermore, small size,
high fecundity, and optically clear development make the zebrafish ideal for high-
throughput screening and chemical testing. These data support the use of zebrafish for
assessing drug safety and toxicity for the hematopoietic and vascular systems. This
chapter provides a review of hematopoiesis and vasculogenesis in the zebrafish, as
well as methods for assays available to test compound-induced toxicity on blood
and endothelial development.

7.2 HEMATOPOIESIS AND VASCULAR
DEVELOPMENT IN THE ZEBRAFISH

7.2.1 Hematopoietic and Endothelial Progenitors

Primitive blood and vascular cells originate from the mesoderm of the embryo and
form clusters called blood islands (Liao et al., 1997). Bone morphogenic protein
(BMP), among other signals, is responsible for generating blood islands from the
mesoderm tissue (Lengerke et al., 2008). Blood islands form in both the cephalic and