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Open Access Highly Accessed Research article

Microarray analysis of Foxa2 mutant mouse embryos reveals novel gene expression and inductive roles for the gastrula organizer and its derivatives

Owen J Tamplin12, Doris Kinzel3, Brian J Cox1, Christine E Bell4, Janet Rossant125 and Heiko Lickert3*

Author Affiliations

1 Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada

2 Department of Molecular Genetics, Medical Sciences Building, 1 King's College Circle, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

3 Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr 1, 85764 Neuherberg, Germany

4 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

5 Department of Obstetrics and Gynecology, 92 College Street, University of Toronto, Toronto, Ontario, M5G 1L4, Canada

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BMC Genomics 2008, 9:511  doi:10.1186/1471-2164-9-511

Published: 30 October 2008

Abstract

Background

The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE). However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined.

Results

To identify genes specific to the Spemann/Mangold organizer, we performed a microarray-based screen that compared wild-type and Foxa2 mutant embryos at late gastrulation stage (E7.5). We could detect genes that were consistently down-regulated in replicate pools of mutant embryos versus wild-type, and these included a number of known node and DE markers. We selected 314 genes without previously published data at E7.5 and screened for expression by whole mount in situ hybridization. We identified 10 novel expression patterns in the node and 5 in the definitive endoderm. We also found significant reduction of markers expressed in secondary tissues that require interaction with the organizer and its derivatives, such as cardiac mesoderm, vasculature, primitive streak, and anterior neuroectoderm.

Conclusion

The genes identified in this screen represent novel Spemann/Mangold organizer genes as well as potential Foxa2 targets. Further investigation will be needed to define these genes as novel developmental regulatory factors involved in organizer formation and function. We have placed these genes in a Foxa2-dependent genetic regulatory network and we hypothesize how Foxa2 may regulate a molecular program of Spemann/Mangold organizer development. We have also shown how early loss of the organizer and its inductive properties in an otherwise normal embryo, impacts on the molecular profile of surrounding tissues.