Endoderm Patterning
Figure 1
In situ hybridization to serial sections of a Xenopus gastrula show that Hex and Cerberus are expressed only in the anterior endoderm, in contrast to Sox17, which is expressed in all of the endoderm tissue.
Sox17
Hex
Shortly after endoderm tissue is formed in the early embryo, it becomes patterned, so that some of it gives rise to the foregut while other regions of the endoderm gives rise to the hindgut. The foregut endoderm contains the progenitor cells that will give rise to the liver, pancreas, thyroid and lungs, whereas the hindgut domain gives rise to the intestine. This patterning process, which progressively subdivides the endoderm into organ domains begins during gastrulation and continues throughout early development ensuring that the organs form in the correct position in the body. The molecular mechanisms that control this are poorly understood, but appear to be mediated by a series of growth factors interactions between the endoderm and surrounding mesoderm. One of the first manifestations of this patterning is the asymmetric expression of genes such the homeobox transcription factor Hex in the foregut progenitor cells (Fig. 1). Hex is a homeodomain transcription factor that is essential for anterior endoderm and liver development.
We are trying to understand the molecular mechanisms that pattern the embryonic endoderm into organ domains with a particular focus on the foregut.
Our recent studies have found that different levels of Wnt growth factors in different parts of the embryo is a key step in patterning the endoderm into foregut and hindgut domains. We have shown that Wnt signaling must be repressed in the anterior endoderm and that this promotes foregut development such as liver and pancreas. In contrast high levels of Wnt in the posterior promotes hindgut fate and intestinal differentiation. We have found that the secreted protein Sfrp5, which can bind to Wnt proteins and block their activity, is a key gene in regulating foregut development and that is coordinates cell identity with tissue morphogenesis. Using mouse genetics and transgenic frog embryos, which express Green Fluorescent Protein under the control of the Hex promoter, we are characterizing how Wnts and other growth factors control the genetic program of foregut development. In addition we are using various screens to identify novel genes involved in this process.
These studies will provide essential information on the genetic pathways controlling the earliest steps in the formation of the liver, pancreas and lungs.
For more details see:
Li Y, Rankin SA, Sinner D, Kenney, AP, Krieg PA, Zorn AM. (2008) Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and non-canonical Wnt11 signaling. Genes & Development 22:3050-63.
McLin VA, Rankin SA, Zorn AM. (2007) Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development 134: 2207-2217.
Costa JMB, Mason J, Lee M, Amaya E, Zorn AM. (2003) Novel gene expression domains reveal early patterning of the Xenopus endoderm. GEP 3: 509-519.
Zorn AM, Butler K, Gurdon JB. (1999) Anterior Endomesododerm Specification in Xenopus by Wnt/β-catenin and TGFβ Signaling Pathways. Dev Biol 209: 282-297.
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 3461.
Division of Developmental Biology
Cincinnati Children's Research Foundation
3333 Burnet Ave.
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.
