Abstract
BackgroundThe 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.ResultsTo 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.ConclusionThe 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.
Highlights
The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers
The embryonic stem (ES) cells contribute to the epiblast and the tetraploid host will contribute to the extra-embryonic tissues, including the visceral endoderm (VE)
We found a number of genes that had weak to no staining at E7.5, but that showed endoderm expression at E8.5 (Cd276, Galt, Gpx2, Pla2g7, Raet1e, Wfdc2; Additional File 3); because the E7.5 microarray screen detected these genes as being significantly reduced, we took this to mean the in situ hybridization lacked sufficient sensitivity at this earlier stage
Summary
The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. The organizer is a highly specialized and transient structure that has been found in all studied vertebrates It was originally discovered in amphibians by Spemann and Mangold in 1924 by its ability to induce much of a secondary body axis when transplanted to a host embryo [1]. The early gastrula organizer (EGO) forms just anterior to the emerging primitive streak (PS) at E6.5, gives rise to the mid-gastrula organizer (MGO) as the PS elongates towards the distal tip of the mouse embryo, and forms the morphologically visible node at E7.5 [5] These organizer cell populations contribute to the axial mesoderm and notochord, and are the source of DE that displaces the embryonic visceral endoderm (VE) into the extra-embryonic region (reviewed [6]). The organizer has been studied for more than 80 years, there are still relatively few genes that have defined expression in this highly specialized tissue
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