Wells Lab

  • Molecular Mechanisms that Establish Organ Domains Along the Anterior-Posterior Axis

    Endoderm patterning is highly conserved across vertebrate species


    Significant progress has been made in understanding how the endoderm is first specified during gastrulation and how specific endoderm organs, once specified, undergo morphogenesis in the developing fetus. However, there is a profound gap in our understanding of how endoderm organ domains are initially established along the A-P axis of the developing gut tube, an obligatory step for endoderm organogenesis. For example, one fundamentally important question is: How are some endoderm cells directed to form the pancreas whereas other cells are directed to form the liver?

    Our lab uses several model organisms, including frogs, chicks and mice, to investigate endoderm patterning. The figure here shows a mouse-to-chick xenograft approach that we developed in the lab to investigate how the endoderm is specified to adopt certain organ lineages along the A-P axis at e7.5 (figure 1). In this experiment, we demonstrated that the mouse endoderm is still plastic at this stage; for example, cells that would normally contribute to the large intestines are re-specified toward a pancreatic fate by grafting it into the pancreatic domain of a chick embryo. This result suggests that endoderm patterning is highly conserved between birds and mammals. In addition, this is a powerful assay to identify the genes and signals that regulate how endoderm cells are specified during 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.

    Bates MD, Wells JM, Venkatesh B. Comparative Genomics of the Hlx Homeobox Gene and Protein. Gene. 6;352:45-56. 2005.

    Wells JM, Melton DA. Early mouse endoderm is patterned by soluble factors from adjacent germ layers. Development. 127:1563-1572. 2000.


 
  • Endoderm organogenesis.
    Endoderm organogenesis.
  • Mouse, chick, and chouse emdoderm.

    click to enlarge

    Mouse, chick, and chouse emdoderm.

    E7.5 mouse endoderm is not specified along the A-P axis. Posterior (intestinal) mouse endoderm is induced to express Pdx1-lacZ (blue cells in chouse) when grafted into the pancreatic domain of the chick embryo. The top panel shows expression of the pancreatic marker Pdx1 in the mouse. The middle panel is a control chick embryo, and the bottom panel shows expression of Pdx1-lacZ in the posterior mouse endoderm that was grafted into chick embryos.