Mice deficient in Hox11 are asplenic. As Hoxll can function as a transcription factor, we examined the spatial and temporal mRNA expression patterns of Hox11 and a candidate target gene, the Wilm's tumor gene Wt1, in the developing spleen. Hox11 mRNA first appears at approximately dE10.5 in the dorsal mesogastrium while Wt1 mRNA is expressed from dE11.5, approximately 24 hours after Hox11 mRNA first appears. Wt1 mRNA was significantly reduced in the spleen anlage of Hox11-null mice suggesting that Wt1 acts downstream of Hox11 in a transcriptional cascade. Additionally, Hox11 protein is able to transactivate the WT1 promoter in a Hox11-null fibroblast cell line. As Wt1-null embryos have recently been reported to be asplenic, these findings suggest that Wt1 and Hox11 may be components common to a genetic hierarchy that is required for spleen development.
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