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 Blood, 1 November 2005, Vol. 106, No. 9, pp. 3004-3011.
Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-02-0461.

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HEMATOPOIESIS

Three pathways to mature macrophages in the early mouse yolk sac

Julien Y. Bertrand, Abdelali Jalil, Michèle Klaine, Steffen Jung, Ana Cumano, and Isabelle Godin

From Institut National de la Santé et de la Recherche Médicale (INSERM) U668, Unité de Développement des Lymphocytes, Institut Pasteur, Paris, France; Service Commun de Microscopie Confocale and INSERM U362, Institut Gustave Roussy, Villejuif, France; and Department of Immunology, Weizmann Institute for Science, Rehovot, Israel.

The existence of macrophages (M{varphi}) of yolk-sac (YS) origin has been reported in all vertebrate models. However, the nature of their precursors and pathways of differentiation have not been elucidated. Phenotypic and differentiation potential analyses of YS at 7.5 to 10 postcoital days (dpc), performed in CX3CR1GFP embryos, allowed us to discern 3 independent M{varphi} populations. A first transient wave consisted of mature, maternal-derived M{varphi}present as early as 7.5 to 8 dpc. A second wave of committed M{varphi} precursors arose at 8 dpc (2-4 somite stage) and was followed by a third wave of erythromyeloid precursors (4-6 somite stage). Both types of precursors displayed similar phenotypes and gave rise to CX3CR1/green fluorescent protein (GFP)–positive M{varphi}, but differed by their differentiation potential, at the clonal level. The combined data of phenotypic, gene-expression, and in situ analyses allowed us to conclude that the previously named "primitive M{varphi}" corresponded to a mixture of the first transient wave and committed M{varphi} precursors. Both YS-derived precursors followed a developmental pathway common to adult M{varphi} and could be qualified as definitive.


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