HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bouzin, C. Articles by Rousseau, G. G. Search for Related Content PubMed PubMed Citation Articles by Bouzin, C. Articles by Rousseau, G. G.

The Onecut Transcription Factor Hepatocyte Nuclear Factor-6 Controls B Lymphopoiesis in Fetal Liver¹

Caroline Bouzin^*, Frédéric Clotman^*, Jean-Christophe Renauld, Frédéric P. Lemaigre^* and Guy G. Rousseau^2,*

^* Hormone and Metabolic Research Unit, Université Catholique de Louvain and Institute of Cellular Pathology, Brussels, Belgium; and Experimental Medicine Unit, Ludwig Institute for Cancer Research, Brussels, Belgium

Mouse genetic models have helped to identify transcription factors that are expressed by hemopoietic cells and control their differentiation into lymphoid cells. However, little is known on transcription factors that are involved in this process, but are expressed in nonhemopoietic cells of the microenvironment. We show in this study that inactivation of the gene coding for hepatocyte nuclear factor-6 (HNF-6) in mice led to B lymphopenia in the bone marrow and spleen. This phenotype disappeared shortly after birth when fetal B lymphopoiesis is no longer active, pointing to a defect in fetal liver. Indeed, the number of B cells was decreased in this organ as well. An analysis of B cell developmental markers in fetal liver cells showed that B lymphopoiesis was impaired just beyond the pre-pro B cell stage. Hemopoietic cells from hnf6^-/- fetal liver could reconstitute the lymphoid system when injected into scid mice. Because parenchymal cells, but not hemopoietic cells, expressed hnf6 in normal liver, we concluded that HNF-6 controls B lymphopoiesis in fetal liver and that HNF-6 exerts this control indirectly by acting in parenchymal cells. The involvement, in the B cell defect of hnf6^-/- fetuses, of genes known to exert such an indirect control was ruled out by expression analysis, including microarrays, and by in vivo rescue experiments. This work identifies HNF-6 as the first noncell-intrinsic transcription factor known to control B lymphopoiesis specifically in fetal liver.

This article has been cited by other articles:

				Z. Lin, D. K. Crockett, S. D. Jenson, M. S. Lim, and K. S. J. Elenitoba-Johnson Quantitative Proteomic and Transcriptional Analysis of the Response to the p38 Mitogen-activated Protein Kinase Inhibitor SB203580 in Transformed Follicular Lymphoma Cells Mol. Cell. Proteomics, August 1, 2004; 3(8): 820 - 833. [Abstract] [Full Text] [PDF]