Cincinnati Children's Hospital Medical Center Logo

Wells Lab

Why Study Endoderm Development?

In this country alone, defective endoderm development results in 3400 children/year being born with congenital gastro-intestinal malformations. Additional diseases affecting endodermal organs include Juvenile Diabetes, which results from the autoimmune destruction of pancreatic beta cells. In light of this, surprisingly little is known about how early endoderm cells obtain positional identity along the anterior-posterior (A-P) axis, nor how this regional identity lays down the blue print for where organs will form in the developing gastrointestinal and respiratory tracts. After gastrulation in mouse (7.5 days after fertilization), the endoderm is a one cell-layer thick sheet of approximately 500-1000 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 hematopoesis. A better understanding of endoderm development will facilitate the discovery of new molecular diagnostics and stem cell-based therapeutics for human diseases affecting endodermal organs.

Figure 1. Endoderm organ development.
Figure 1: Endoderm organ development. Top - mouse embryos at e7.5, e8.5 and e10.5 days an adult mouse pancreas. Bottom - endoderm (yellow) organogenesis. Endoderm is 500-1000 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.) and pancreas (dorsal and ventral pancreas) (e10.5). The e10.5 embryo and adult islets express betagalactosidase under control of the Pdx1 gene (animals from Chris Wright, Vanderbilt University).

 

Relevant Publications and Review Articles

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

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

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

Wells JM, Melton DA. Vertebrate endoderm development Annu. Rev. Cell Dev. Biol., 15: 393-410. (304kb .pdf file) 1999

For more information about early mouse development, visit the Society for Developmental Biology.