Hox11 acts cell autonomously in spleen development and its absence results in altered cell fate of mesenchymal spleen precursors.
The genetic steps governing development of the spleen are largely unknown. Absence of Hox11 in mice results in asplenia, but it is unclear how Hox11 exerts its effect on spleen development. To more precisely define Hox11's role in spleen morphogenesis, we have examined the fate of the developing spleen in Hox11(-/-) mice. Perturbation of spleen development begins between dE13 and dE13.5. Cells of the spleen anlage persist past this developmental stage as an unorganized rudiment between the stomach and the pancreas. They fail to proliferate, and haematopoietic cells do not colonize the rudiment. At later stages of embryonic development, the cells can be observed in the mesenchyme of the pancreas, also an expression site of Hox11. In Hox11-/-<-->+/+ chimaeras, spleens were devoid of Hox11(-/-) cells, indicating that the genetic defect is cell autonomous and not due to failure of the organ anlage to attract and retain haematopoietic cells. In -/-<-->+/+ chimaeric embryos, Hox11(-/-) cells were initially present in the spleen anlage. However, at dE13, a reorganization of the spleen occurred in the chimaeras and Hox11(-/-) cells were subsequently excluded from the spleen, suggesting that a change in the affinity for one of the spleen cells had occurred. These observations demonstrate that spleen development consists of genetically separable steps and that absence of Hox11 arrests spleen development at an early stage. The formation of the spleen primordium before the entry of haematopoietic cells does not require the activity of Hox11. However, subsequent differentiation of spleen precursor cells is dependent on the Hox11 gene.
Kanzler
B
B
Department of Developmental Immunology, Max-Planck Institute for Immunobiology, Stuebeweg 51, Freiburg, 79108, Germany.
Dear
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TN
D000818:Animals; D002449:Cell Aggregation; D002454:Cell Differentiation; D002678:Chimera; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains; D009028:Morula; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000196:embryology*; D013234:Stem Cells
D018398:Homeodomain Proteins; D015513:Oncogene Proteins; C487378:Tlx1 protein, mouse