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Translocator protein (18 kDa) is involved in primitive erythropoiesis in zebrafish

Christine Rampon^*,,1, Mohamed Bouzaffour^*,, Mariano A. Ostuni^*,, Pascale Dufourcq^*,, Christelle Girard, Jean Marie Freyssinet, Jean-Jacques Lacapere^*,, Ghislaine Schweizer-Groyer and Sophie Vriz^*,

^* University of Denis Diderot-Paris 7, Paris, France;

INSERM U770 and

INSERM U788, Le Kremlin-Bicêtre, France, and University of Paris-sud 11, Orsay, France; and

INSERM U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, Paris, France

¹ Correspondence and current address: CNRS UMR 8542, Chaire des Processes Morphogénètiques, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France. E-mail: christine.rampon{at}college-de-france.fr

The translocator protein (18 kDa) (TSPO), also known as peripheral-type benzodiazepine receptor, is directly or indirectly associated with many biological processes. Although extensively characterized, the specific function of TSPO during development remains unclear. It has been reported that TSPO is involved in a variety of mechanisms, including cell proliferation, apoptosis, regulation of mitochondrial functions, cholesterol transport and steroidogenesis, and porphyrin transport and heme synthesis. Although the literature has reported a murine knockout model, the experiment did not generate information because of early lethality. We then used the zebrafish model to address the function of tspo during development. Information about spatiotemporal expression showed that tspo has a maternal and a zygotic contribution which, during somatogenesis, seems to be erythroid restricted to the intermediate cell mass. Genetic and pharmacological approaches used to invalidate Tspo function resulted in embryos with specific erythropoietic cell depletion. Although unexpected, this lack of blood cells is independent of the Tspo cholesterol binding site and reveals a new in vivo key role for Tspo during erythropoiesis.—Rampon, C., Bouzaffour, M., Ostuni, M. A., Dufourcq, P., Girard, C., Freyssinet, J. M., Lacapere, J.-J., Schweizer-Groyer, G., Vriz, S. Translocator protein (18 kDa) is involved in primitive erythropoiesis in zebrafish.

Key Words: peripheral-type benzodiazepine receptor • hematopoiesis • transcription factor GATA-1