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).
To date we have identified several direct transcriptional targets of Sox17. We further show that -catenin, physically interacts with Sox17 and potentiates its transcriptional activation of target genes. This data suggests that in a mechanism analogous to Tcf/Lef interacting with β-catenin, Sox17 and β-catenin interact to transcribe endodermal target genes.
In our ongoing research we are using a number of genomic resources including functional screens in Xenopus tropicalis and DNA-microarrays to define the entire genetic program controlled by Sox17 and the other transcription factors that regulate Endoderm formation.
Learn more about Sox17 and endoderm specification.
Related Publications
Zorn, AM, Barish, G, Williams, B, Lavander, P, Klymkowsky, M and 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.
D'Souza A, Lee M, Taverner N, Mason J, Carruthers S, Smith JC, Amaya E, Papalopulu N and Zorn AM. (2003) Molecular components of the endoderm specification pathway in Xenopus tropicalis. Dev. Dyn. 226: 118-127
Gilchrist M, Zorn AM, Voigt J, Smith JC, Papalopulu N, and Amaya E (2004) Defining a large set of full length clones from a Xenopus tropicalis EST project. Dev. Bio. 271: 498-516
Sinner D, Rankin S, Lee M and Zorn AM (2004) Sox17 and β-catenin cooperate to regulate the transcription of enododermal genes. Development 131: 3069-3080
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"
Zorn AM and Wells JM (2007) Molecular basis of vertebrate endoderm development. International Review of Cytology 259:49-111
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@chmcc.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.
