Wells Lab

  • Molecular Pathways that Establish the Foregut, Midgut and Hindgut Domains

    What are the molecular mechanisms that specify A-P endoderm pattern at this stage in development?

    We have used both in vitro and in vivo analyses to identify that FGF4-mediated signaling plays a role in establishing gut tube domains in two ways. FGF4 represses foregut fate between the gastrula and early somite stages while at the same time promoting midgut and hindgut fate in a graded fashion.

    Currently, we are using chick and mouse embryos and human endoderm cultures (from differentiated embryonic stem cells) to identify how FGF signaling directs posterior endoderm patterning in vivo. We have recently begun to investigate how FGF pathways interact with other posterior pathways including the Wnt pathway (in collaboration with Aaron Zorn). Establishing these gene expression domains during gut tube patterning is critical for subsequent stages of endoderm organogenesis.

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    Relevant Publications

    Moore-Scott BA, Opoka R, Kordich JJ, Lin S, Wells JM. Identification of molecular markers that are expressed in discrete anterior-posterior domains of the endoderm from the gastrula stage to mid-gestation. Dev Dyn. 1997-2003. 2007.

    Dessimoz J, Kordich JJ, Opoka R, Grapin-Botton A,Wells JM. FGF signaling is necessary for establishing gut tube domains along the anterior-posterior axis in vivo. Mech Dev. 123(1):42-55. 2006.

    Serls AE, Doherty S, Parvatiyar P,Wells JM, Deutsch GH. Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung. Development, 132:35-47. 2005.

  • Endoderm patterning.

    click to enlarge

    Endoderm patterning.

    Early endoderm patterning along the A-P axis is critical for fetal gut development.

    Top panel: Early somite stage chick embryo at early stages of endoderm patterning. FGF4 and Wnt3 are expressed in posterior mesoderm.

    Bottom panel: Patterned E8.5 gut tube. Gene expression is now restricted to early organ domains along A-P axis. Nkx2.1 (green), Hex 1 (red), Pdx1 (orange) and Cdx2 and Cdx4 (blue).