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Blood, 1 January 2008, Vol. 111, No. 1, pp. 132-141.
Prepublished online as a Blood First Edition Paper on September 17, 2007; DOI 10.1182/blood-2007-06-095398.
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Submitted June 14, 2007
Accepted September 12, 2007
Origins and unconventional behavior of neutrophils in developing zebrafish
Dorothee Le Guyader, Michael J Redd, Emma Colucci-Guyon, Emi Murayama, Karima Kissa, Valerie Briolat, Elodie Mordelet, Agustin Zapata, Hiroto Shinomiya, and Philippe Herbomel*
Unite Macrophages et Developpement de l'Immunite, CNRS-URA 2578, Institut Pasteur, Paris, France
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Department of Immunology and Host Defenses, Ehime University School of Medicine, Ehime, Japan
* Corresponding author; email: herbomel{at}pasteur.fr.
The first leukocytes that arise in the development of vertebrate embryos are the primitive macrophages, which differentiate in the yolk sac, and then quickly invade embryonic tissues. These macrophages have been considered to constitute a separate lineage giving rise to no other cell type. Using an in vivo photoactivatable cell tracer in the transparent zebrafish embryo, we demonstrate that this lineage also gives rise to an equal or higher number of neutrophilic granulocytes. Surprisingly, the differentiation of these primitive neutrophils occurs only after primitive myeloid progenitors have dispersed in the tissues. By 2 days post-fertilization, these neutrophils have become the major leukocyte type found wandering in the epidermis and mesenchyme. Like the primitive macrophages, all primitive and larval neutrophils express PU.1 and L-plastin, they are highly attracted to local infections, yet only a small fraction of them phagocytose microbes, and to a much lesser extent per cell than the macrophages. They are also attracted to variously stressed or malformed tissues, suggesting a wider role than anti-microbial defence.

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