Hox11 controls the genesis of the spleen

Abstract

Many homeobox genes are clustered in a linear array along a chromosome, reflecting their ordered expression along the anterior-posterior axis of the embryo. Expression patterns as well as grafting, ectopic expression and loss-of-function experiments suggest that the Hox genes encode a combinatorial system of positional specification along that axis. In contrast, the function of orphan homeobox genes located at sites outside the four mammalian Hox clusters is less well understood. To assess the functional role of the orphan homeobox gene Hox11, we have generated Hox11-deficient mice through gene targeting. Hox11-/- mice have no spleen, but otherwise appear normal. Hox11 is normally expressed in the splenic anlage arising from the splanchnic mesoderm. Hox11-/- embryos have no cellular organization at the site of splenic development but all other splanchnic derivatives develop normally. Hox11 controls the genesis of a single organ, providing new insight into the genetic regulation of morphogenesis.

Targeted disruption of the homeobox transcription factor Bapx1 results in lethal skeletal dysplasia with asplenia and gastroduodenal malformation

“…Hox11-de®cient mice also displayed asplenia (Roberts et al 1994;Dear et al 1995). We investigated the Hox11 expression in E13.5 Bapx1 À/± embryos by in situ hybridization.…”

Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

“…Homeodomain proteins not found within these four chromosomal clusters, including Gtx, constitute a diverse set of transcription factors, many of which are expressed in a tissueor organ-specific manner (Blochlinger et al, 1988;Ingraham et al, 1988;Staudt et al, 1988;Suh et al, 1994). Although down- stream or target genes have not been identified for many of these orphan homeodomain proteins, several of them have been implicated in organogenesis and cell differentiation (Roberts et al, 1994;Slack, 1995). The homeodomain protein most closely related to Gtx is Nkx6.1, a hamster protein of the N K-class of homeodomain proteins, isolated from a pancreatic ␤-cell cDNA library (Rudnick et al, 1994).…”

A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

“…Besides these clustered homeobox genes, certain of the unclustered and more divergent homeobox genes have been assigned roles in growth control, organogenesis, or establishment of cellular phenotypes (2)(3)(4)(5). Indeed, one of the unclustered homeobox gene, HOX11 (6)(7)(8)(9), controls the genesis of spleen (10,11). The Ncx/Hox11L.1 gene, belonging to the Hox11 gene family (12,13), is also mapped outside the clustered homeobox gene on mouse chromosome (14).…”