The splanchnic mesodermal plate directs spleen and pancreatic laterality,and is regulated byBapx1/Nkx3.2

Abstract

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.

Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1−/− mice

“…Apart from being important for interaction with underlying epithelium, the mesenchyme surrounding the dorsal pancreas also contributes to development of the spleen during early stages of development ( Fig. 1A; Kanzler and Dear 2001;Hecksher-Sorensen et al 2004).The mammalian homeobox gene Bapx1 (Nkx3.2) encodes a putative transcription factor that belongs to the Nkx gene family, most similar to the Drosophila homolog bap (Kim and Nirenberg 1989). Bapx1-null mutants show visceral mesoderm defects manifesting as asplenia and impaired pyloric sphincter formation (Lettice et al 1999;Tribioli and Lufkin 1999;Akazawa et al 2000).…”

“…Apart from being important for interaction with underlying epithelium, the mesenchyme surrounding the dorsal pancreas also contributes to development of the spleen during early stages of development ( Fig. 1A; Kanzler and Dear 2001;Hecksher-Sorensen et al 2004).…”

Identification of novel genes and transcription factors involved in spleen, thymus and immunological development and function

“…1,4 By E13.5, the splenic primordium is visible as a ridge of cells on the dorsal stomach. A normally developing spleen can no longer be seen at this time in Hox11 À/À , capsulin À/À and Bapx1 À/À mice, [1][2][3]5 confirming the critical role of these transcription factors in spleen organogenesis. The first hematopoietic cells begin to appear in the spleen anlage, and between E13.5 and approximately E16.5, the spleen is a site of hematopoiesis in the fetus.…”

“…By E11.5, the expression of several transcription factors essential to spleen organogenesis including Hox11, Nkx2.5, capsulin/Pod-1, Wt1 and Bapx1 can be detected. [1][2][3] The molecular hierarchy regulating expression of these transcription factors, and the pathways they function within, are only beginning to be established. 1,4 By E13.5, the splenic primordium is visible as a ridge of cells on the dorsal stomach.…”

Multimodal imaging of mouse development: Tools for the postgenomic era

“…Both EFIC and OPT have been used to evaluate development in normal and mutant mouse embryos in several studies, and the reconstruction of complex 3D structures has revealed subtle changes in structure (Weninger and Mohun, 2002;Hecksher-Sorensen et al, 2004;Lickert et al, 2004;Meilhac et al, 2004;Rosenthal et al, 2004;Smyth et al, 2004;Wilkie et al, 2004;Takeuchi et al, 2005a;Weninger et al, 2005). The ability to collect 3D gene and protein expression data also makes it possible to create searchable atlases of expression data (Sarma et al, 2005), allowing for a greater appreciation of how changes in 3D morphology relate to changes at a molecular level.…”