Wells Lab
Why Do We Study Endoderm Development?

Why Study Endoderm Development?

The endoderm is one of 3 primary germ layers of the vertebrate embryo.

In the United States alone, defective endoderm development results in 3400 children per year being born with congenital gastro-intestinal malformations. In addition, some of the most common and costly diseases such as Diabetes and digestive diseases affect endodermal organs such as the pancreas, liver, stomach, and intestines.

In light of this, many years of effort have gone into identifying how endodermally derived organs normally form, and how genetic mutations and chemical teratogens cause birth defects.

Until recently, therapeutic options to treat birth defects have been limited. However, due to tremendous advances in our understanding of organ development, we are now able to grow human organ tissues called organoids through the directed differentiation of pluripotent stem cells.

Moreover, using tools to genetically manipulate human cells, it is now possible to genetically correct disease-causing mutations and grow healthy human tissue in vitro.

While we are still years away from growing complete organs such as the stomach, intestine, and colon, simpler structures such as pancreatic endocrine cells have been generated from human pluripotent stem cells and are being tested for safety and therapeutic efficacy in patients with type-1 diabetes.

Through the collaborative efforts of basic scientists and clinicians, cell and tissue replacement therapies for other digestive diseases are intensively being developed.  

Endoderm organ development.

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Zorn & Wells Figure 1. Overview and timeline of endoderm organ formation. The major events in endoderm organ formation are listed in chronological order and (b) illustrated with images of mouse embryos at e7.5 (top), e8.5, and e9.5 of development, with the endoderm shaded in (yellow). A schematic of a cross section through the e9.5 embryo illustrates the characteristic arrangement of the germ layers with the endoderm lining the gut tube (yellow), surrounded by mesoderm (red), and ectoderm (blue). (c) Endoderm cell lineages projected on to a schematic of the gastrointestinal tract. Fg; foregut, mg; midgut and hg; hindgut. From Zorn and Wells, Ann. Rev. Cell and Dev. Bio. 2009.