The splanchnic mesodermal plate directs spleen and pancreatic laterality, and is regulated by Bapx1/Nkx3.2.
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.
Comparative and Developmental Genetics Section, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Jacob
J
Hecksher-Sørensen
Robert P
RP
Watson
Laura A
LA
Lettice
Palle
P
Serup
Lorraine
L
Eley
Carlo
C
De Angelis
Ulf
U
Ahlgren
Robert E
RE
Hill
D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002455:Cell Division; D004848:Epithelium / Q000196:embryology; D051526:Fibroblast Growth Factor 10; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009024:Morphogenesis; D010179:Pancreas / Q000002:abnormalities / Q000196:embryology*; D015398:Signal Transduction; D013154:Spleen / Q000002:abnormalities / Q000196:embryology*; D013270:Stomach / Q000196:embryology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D014714:Vertebrates / Q000196:embryology
C496464:Fgf10 protein, mouse; C496460:Fgf9 protein, mouse; D051526:Fibroblast Growth Factor 10; D051525:Fibroblast Growth Factor 9; D018398:Homeodomain Proteins; C107965:Nkx3-2 protein, mouse; D014157:Transcription Factors; D005346:Fibroblast Growth Factors