Endoderm Specification
The endoderm gives rise to the epithelial lining of the respiratory and gastrointestinal tract as well as to the liver, lungs, pancreas, thyroid and thymus. Recent studies have resulted a model of the molecular pathway that specifies the endoderm during gastrulation. This pathway appears to be largely conserved between mammals, frogs (Xenopus) and zebrafish and includes activity of a number of transcription factors and growth factors of the nodal family. The HMG box transcription factor Sox17 is a key component of this pathway and is essential for endoderm formation, however, the molecular events controlled by Sox17 are largely unknown. We are trying to address the following questions:
- What is the precise role of Sox17 in endoderm development?
- What is the genetic program controlled by Sox17?
- What is the relationship between Sox17 and the other transcription factors and growth factors that specify the endodermal precursors?
- How does Sox17 biochemically interact with growth factor signaling pathways to regulate the expression of its target genes?
Figure 1
On the left, a section of an early blastula shows a group of several hundred presumptive endodermal cells (orange), that ultimately give rise to the entire GI tract and associated organs (middle). A vast array of highly specialized epithelial cell types are present in the GI tract, as illustrated by a histological section of the gal bladder (on the right).
Using global micro-array analyses we recently identified most of the gene expressed in the forming endoderm during Xenopus gastrulation, including the entire genetic program regulated by Sox17. Our studies have also shown that Sox17 physically interacts with beta-catenin, which is a key component of the components of the Wnt signaling pathway, and this enhances the ability of Sox17 to activate transcription of its target genes. We have also found that many Sox factors interact with beta-catenin/Tcf and modulate cellular responses to Wnt growth factor signaling - a finding that may have broad implications for diseases such as cancer.
On going studies are focused on elucidating the role of novel Sox17-target genes and examining the molecular mechanisms by which Sox proteins interact with the canonical Wnt signaling pathway.
Learn more about Sox17 and endoderm specification.
Related Publications
Woodland HR, Zorn AM. (2008) The core endodermal gene network of vertebrates: Combining developmental precision with evolutionary flexibility. BioEssays 30:1-9.
Sinner D, Kordich JJ, Opoka R Rankin SA, Lin S-J, Jonatan D, Zorn AM*, Wells JM*. (2007) Sox17 and Sox4 differentially regulate beta-catenin/TCF activity and proliferation of carcinoma cells. Mol Cell Biol 27:7802-7815. (PMC2169141)
Zorn AM, Wells JM. (2007) Molecular basis of vertebrate endoderm development. International Review of Cytology 259:49-111.
Sinner D, Kirilenko P, Rankin S, Wei E, Howard L, Kofron M, Heasman J, Woodland HR, Zorn AM (2006) Global analysis of the transcriptional network controlling Xenopus endoderm formation. Development 133:19555-1966. *This paper was selected by the "Faculty of 1000"
Sinner D, Rankin S, Lee M, Zorn AM. (2004) Sox17 and β-catenin cooperate to regulate the transcription of enododermal genes. Development 131:3069-3080.
Gilchrist M, Zorn AM, Voigt J, Smith JC, Papalopulu N, Amaya E. (2004) Defining a large set of full length clones from a Xenopus tropicalis EST project. Dev Bio 271:498-516.
D'Souza A, Lee M, Taverner N, Mason J, Carruthers S, Smith JC, Amaya E, Papalopulu N, Zorn AM. (2003) Molecular components of the endoderm specification pathway in Xenopus tropicalis. Dev Dyn 226:118-127.
Zorn AM, Barish G, Williams B, Lavander P, Klymkowsky M, Varmus HE. (1999) Regulation of Wnt signalling by a Sox protein: XSox17a/b and XSox3 phyically interact with β-catenin. Molecular Cell 4:487-498.
If you would like to join our research team, contact the Zorn Laboratory. The Zorn Lab is part of the Division of Developmental Biology at Cincinnati Children's Research Foundation. The lab is located in Location R (Research Foundation Building), Room 2509.
Division of Developmental Biology
Cincinnati Children's Research Foundation
Cincinnati, OH 45229-3039
E-mail Aaron.Zorn@cchmc.org
Phone 513-636-3770
Fax 513-636-4317 Interested in joining us as a student or a postdoc? Learn more about postdoctoral training and graduate student opportunities at Cincinnati Children's.
