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First published online 25 August 2004
doi: 10.1242/dev.01364
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1 Comparative and Developmental Genetics Section, MRC Human Genetics Unit,
Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
2 Department of Developmental Biology, Hagedorn Research Institute, Niels
Steensens Vej 6, 2820 Gentofte, Denmark
3 The Institute of Human Genetics, The International Centre for Life, Central
Parkway, Newcastle upon Tyne NE1 3BZ, UK
Author for correspondence (e-mail:
bob.hill{at}hgu.mrc.ac.uk)
Accepted 19 July 2004
The mechanism by which left-right (LR) information is interpreted by organ primordia during asymmetric morphogenesis is largely unknown. We show that spleen and pancreatic laterality is dependent on a specialised, columnar mesodermal-derived cell layer referred to here as the splanchnic mesodermal plate (SMP). At early embryonic stages, the SMP is bilateral, surrounding the midline-located stomach and dorsal pancreatic bud. Under control of the LR asymmetry pathway, the left SMP is maintained and grows laterally. Mice carrying the dominant hemimelia (Dh) mutation lack the SMP. Significantly, the mice are asplenic and the pancreas remains positioned along the embryonic midline. In the absence of Fgf10 expression, the spleno-pancreatic mesenchyme and surrounding SMP grow laterally but contain no endodermal component, showing that leftward growth is autonomous and independent of endoderm. In the Bapx1/ mutants, the SMP is defective. Normally, the SMP is a source for both Fgf9 and Fgf10; however, in the Bapx1 mutant, Fgf10 expression is downregulated and the dorsal pancreas remains at the midline. We conclude that the SMP is an organiser responsible for the leftward growth of the spleno-pancreatic region and that Bapx1 regulates SMP functions required for pancreatic laterality.
Key words: LR asymmetry, Bapx1, Pancreas, Spleen, SMP, Fgf regulation, Mouse
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