Hox11 is required to maintain normal Wt1 mRNA levels in the developing spleen

• Published in: Developmental dynamics 2000-05, Vol.218 (1), p.201-206
• Main Authors: Koehler, Katja, Franz, Tanna, Dear, T. Neil
• Format: Article
• Language: English
• Subjects: Animals; asplenia; Cell Line; DNA-Binding Proteins - genetics; dorsal mesogastrium; Female; Gene Expression Regulation, Developmental - physiology; Genes, Reporter; homeobox; Homeodomain Proteins - genetics; Hox11; In Situ Hybridization; Luciferases - genetics; Male; Mice; Mice, Mutant Strains; Oncogene Proteins - genetics; Pregnancy; Promoter Regions, Genetic - physiology; RNA, Messenger - analysis; Spleen - abnormalities; Spleen - embryology; Transcription Factors - genetics; Transcription, Genetic - physiology; Wilm's tumor; Wt1; WT1 Proteins
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/(SICI)1097-0177(200005)218:1<201::AID-DVDY18>3.0.CO;2-R

Mice deficient in Hox11 are asplenic. As Hox11 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. Dev Dyn;218:201–206. © 2000 Wiley‐Liss, Inc.