Wells Lab

  • Why Do We Study Endoderm Development?

    In this country alone, defective endoderm development results in 3,400 children a year being born with congenital gastrointestinal malformations.

    Examples of diseases affecting endodermal organs, such as the pancreas, biliary system and intestine, include juvenile diabetes, biliary atresia and Crohn’s disease. Surprisingly little is known about how early endoderm cells obtain positional identity along the anterior-posterior (A-P) axis, or how this regional identity lays down the blueprint for where organs will form in the developing gastrointestinal and respiratory tracts.

    After gastrulation in mice (7.5 days after fertilization), the endoderm is a one-cell-layer thick sheet of approximately 500-1,000 cells that will form the epithelial lining of the esophagus, lungs, stomach and intestines, and is a major component of many glands including the thyroid, thymus, pancreas and liver. Some endodermal functions include glucose homeostasis, gas exchange, taste, digestion, nutrient absorption, detoxification, blood clotting and hematopoiesis.

    A better understanding of endoderm development has proven seminal for discovery of molecular diagnostics of birth defects and for recent advances in directing stem cell differentiation into pancreas, liver and intestinal tissue.

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    Relevant Publications

    Mayhew CN, Wells JM. Converting human pluripotent stem cells into beta cells: recent advances and future challenges. Curr Opin Organ Transplant. 15:54-60. 2009.

    Zorn AM, Wells JM. Vertebrate endoderm development and organ formation. Annu Rev Cell Dev Biol. 25:221-51. 2009.

    Sinner D, Wells JM, Zorn AM. Principals of Developmental Genetics, Chapter 14: Endoderm Formation. 295-315. Edited by Sally A. Moody. Elsevier Press. 2007.

    Spence JR, Wells JM. Translational embryology: using embryonic principles to generate pancreatic endocrine cells from embryonic stem cells. Dev Dyn. 236:3218. 2007.

    Moore-Scott B, Wells JM. Principals of Developmental Genetics, Chapter 40: Patterning the embryonic endoderm into presumptive organ domains. 909-931. Edited by Sally A. Moody. Elsevier Press. 2007.

    Zorn AM, Wells JM. Molecular basis of vertebrate endoderm development. Int Rev Cytol: a Survey of Cell Biology. 259:49-111. 2007.

    Wells JM, Melton DA. Vertebrate endoderm development. Annu. Rev. Cell Dev. Biol., 15:393-410. 1999.


 
  • Endoderm organ development.

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    Endoderm organ development.

    Endoderm organ development. Top: Mouse embryos at e7.5, e8.5 and e10.5 days from an adult mouse pancreas. Bottom: Endoderm (yellow) organogenesis. Endoderm is 500-1,000 cells on the outside of the e7.5 embryo that forms a primitive gut tube (e8.5) that forms the stomach (St), intestines (Int), trachea, lungs (Lu), liver (Li), gall bladder / biliary tree (GB) and pancreas (dorsal and ventral pancreas) (e10.5). The e10.5 embryo and adult islets express beta-galactosidase under control of the Pdx1 gene. (Animals from Chris Wright, Vanderbilt University).