The dynamics of spleen morphogenesis

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.03.031 Byline: Sally F. Burn (a), Marit J. Boot (a), Carlo de Angelis (a), Roisin Doohan (b), Carlos G. Arques (b), Miguel Torres (b), Robert E. Hill (a) Keywords: Spleen; Nkx2-5; Bapx1; Mouse embryo; Morphogenesis; Gut culture 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. Author Affiliation: (a) Medical and Developmental Genetics Section, MRC Human Genetics Unit, Edinburgh, EH4 2XU, UK (b) Departamento de Biologia del Desarrollo Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, E-28029 Madrid, Spain Article History: Received 11 February 2008; Revised 17 March 2008; Accepted 18 March 2008