Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene Review:

sox17 - SRY-box containing gene 17

Danio rerio

Poulain, M., Reim, G., Alexander, J., Kikuchi, Y., Poulain, M., et al.

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High impact information on sox17

Epistasis experiments are consistent with an instructive role for cas in endoderm formation downstream of Nodal signals and upstream of sox17 [1].
In this report, we first show that the zebrafish bonnie and clyde (bon) gene plays a critical early role in endoderm formation. bon mutants exhibit a profound reduction in the number of sox17-expressing endodermal precursors formed during gastrulation, and, consequently, a profound reduction in gut tissue at later stages [2].
We found that FGF/ERK signalling causes phosphorylation of Casanova/Sox32, an important regulator of endoderm determination, and provide evidence that this phosphorylation attenuates its ability to induce sox17 [3].
Bon/Mixer and Gata5 require Casanova in order to promote endoderm formation and all three factors act upstream of sox17, but it is not clear whether Casanova acts downstream of or in parallel to Bon/Mixer and Gata5 [4].
Injection of antisense Morpholino oligonucleotides targeted against mezzo into bonnie and clyde mutant embryos abolishes all sox17 expression and aggravates their mutant phenotype [4].

Anatomical context of sox17

Zebrafish endoderm differentiation starts with the activation of sox17 by casanova (cas) [5].
These data indicate that Gata5 is involved both in the generation of endodermal cells at late blastula stages and in the maintenance of endodermal sox17 expression during gastrulation [6].

Regulatory relationships of sox17

Overexpression of mixer induces ectopic sox17-expressing cells in wild-type embryos and promotes endoderm formation in oep mutants, but does not rescue sox17 expression or endoderm formation in casanova mutants [7].

Other interactions of sox17

Further, MZspg mutants do not maintain expression of sox32/casanova, express little or no sox17, and fail to develop endodermal tissue [8].
Activation of Notch signaling from an early stage leads to a reduction of endodermal cells, as assessed by sox17 and foxA2 expression [9].
Overexpression of a constitutively active form of the type I transforming growth factor beta (TGF-beta) receptor TARAM-A also promotes sox17 expression in wild-type and oep mutant embryos, but not in casanova mutants [7].
Overexpression of mezzo mRNA can induce ectopic expression of casanova and sox17 and can also turn on the pan mesodermal marker gene ntl [4].

Analytical, diagnostic and therapeutic context of sox17

Cell transplantations show that spg acts in early endodermal precursors, and cas mRNA-injection into MZspg embryos does not restore endoderm development. spg and cas together are both necessary and sufficient to activate endoderm development, and stimulate expression of a sox17 promoter-luciferase reporter [5].

References

A crucial component of the endoderm formation pathway, CASANOVA, is encoded by a novel sox-related gene. Dickmeis, T., Mourrain, P., Saint-Etienne, L., Fischer, N., Aanstad, P., Clark, M., Strähle, U., Rosa, F. Genes Dev. (2001)
The zebrafish bonnie and clyde gene encodes a Mix family homeodomain protein that regulates the generation of endodermal precursors. Kikuchi, Y., Trinh, L.A., Reiter, J.F., Alexander, J., Yelon, D., Stainier, D.Y. Genes Dev. (2000)
Zebrafish endoderm formation is regulated by combinatorial Nodal, FGF and BMP signalling. Poulain, M., Fürthauer, M., Thisse, B., Thisse, C., Lepage, T. Development (2006)
Mezzo, a paired-like homeobox protein is an immediate target of Nodal signalling and regulates endoderm specification in zebrafish. Poulain, M., Lepage, T. Development (2002)
The POU domain protein spg (pou2/Oct4) is essential for endoderm formation in cooperation with the HMG domain protein casanova. Reim, G., Mizoguchi, T., Stainier, D.Y., Kikuchi, Y., Brand, M. Dev. Cell (2004)
Multiple roles for Gata5 in zebrafish endoderm formation. Reiter, J.F., Kikuchi, Y., Stainier, D.Y. Development (2001)
A molecular pathway leading to endoderm formation in zebrafish. Alexander, J., Stainier, D.Y. Curr. Biol. (1999)
Zebrafish pou5f1/pou2, homolog of mammalian Oct4, functions in the endoderm specification cascade. Lunde, K., Belting, H.G., Driever, W. Curr. Biol. (2004)
Notch signaling can regulate endoderm formation in zebrafish. Kikuchi, Y., Verkade, H., Reiter, J.F., Kim, C.H., Chitnis, A.B., Kuroiwa, A., Stainier, D.Y. Dev. Dyn. (2004)