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Dev Biol 2016 Aug 01;4161:187-199. doi: 10.1016/j.ydbio.2016.05.025.
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Syndecan4 coordinates Wnt/JNK and BMP signaling to regulate foregut progenitor development.

Temporally and spatially dynamic Wnt and BMP signals are essential to pattern foregut endoderm progenitors that give rise to the liver, pancreas and lungs, but how these two signaling pathways are coordinated in the extracellular space is unknown. Here we identify the transmembrane heparan sulphate proteoglycan Syndecan-4 (Sdc4), as a key regulator of both non-canonical Wnt and BMP signaling in the Xenopus foregut. Foregut-specific Sdc4 depletion results in a disrupted Fibronectin (Fn1) matrix, reduced cell adhesion, and failure to maintain foregut gene expression ultimately leading to foregut organ hypoplasia. Sdc4 is required to maintain robust Wnt/JNK and BMP/Smad1 signaling in the hhex+ foregut progenitors. Pathway analysis suggests that Sdc4 functionally interacts with Fzd7 to promote Wnt/JNK signaling, which maintains foregut identity and cell adhesion. In addition, the Sdc4 ectodomain is required to support Fn1 matrix assembly, which is essential for the robust BMP signaling that promotes foregut gene expression. This work sheds lights on how the extracellular matrix can coordinate different signaling pathways during organogenesis.

PubMed ID: 27235146
PMC ID: PMC5293220
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: a2m atf2 bmp2 bmp4 bmp7.1 cdh1 cdh3 chdh ctnnb1 dvl2 fn1 fzd7 hhex itga5 itgb1 mapk8 nr1h5 pdx1 plin1 prl.2 sdc4 sfrp5 smad1 szl tuba4b wnt11
Antibodies: Cdh3 Ab1 Ctnnb1 Ab2 Fn1 Ab1 Itgb1 Ab1 Mapk8 Ab1 Smad1 Ab12
Morpholinos: cdh3 MO1 fn1 MO1 fn1 MO2 fzd7 MO3 fzd7 MO5 sdc4 MO1 sdc4 MO2 szl MO1

Phenotypes: Xla Wt + PD173074 (Fig S5 A3) [+]

Article Images: [+] show captions
References [+] :
Ahn, FGF2 stimulates the proliferation of human mesenchymal stem cells through the transient activation of JNK signaling. 2009, Pubmed