title: The dynamics of spleen morphogenesis.
abstract: The mammalian spleen has important functions in immunity and haematopoiesis but little is known about the events that occur during its early embryonic development. Here we analyse the origin of the cells that gives rise to the splenic mesenchyme and the process by which the precursors assume their position along the left lateral side of the stomach. We report a highly conserved regulatory element that regulates the Nkx2-5 gene throughout early spleen development. A transgenic mouse line carrying this element driving a reporter gene was used to show that morphogenesis of the spleen initiates bilaterally and posterior to the stomach, before the splenic precursors grow preferentially leftward. In addition the transgenic line was used in an organ culture system to track spleen precursor cells during development. Spleen cells were shown to move from the posterior mesenchyme and track along the left side of the stomach. Removal of tissue from the anterior stomach resulted in splenic cells randomly scattering suggesting a guidance role for the anterior stomach. Using a mouse line carrying a conditional Cre recombinase to mark early precursor cell populations, the spleen was found to derive from posterior mesenchyme distinct from the closely adjacent stomach mesenchyme.
authors.affiliation: Medical and Developmental Genetics Section, MRC Human Genetics Unit, Edinburgh, EH4 2XU, UK.
authors.forename: Sally F
authors.initials: SF
authors.lastname: Burn
authors.forename: Marit J
authors.initials: MJ
authors.lastname: Boot
authors.forename: Carlo
authors.initials: C
authors.lastname: de Angelis
authors.forename: Roisin
authors.initials: R
authors.lastname: Doohan
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Arques
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hill
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D013154:Spleen / Q000166:cytology / Q000196:embryology*; D013270:Stomach / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; C107965:Nkx3-2 protein, mouse; D014157:Transcription Factors