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XB-ART-44317
Development December 1, 2011; 138 (24): 5345-56.

Novel functions of Noggin proteins: inhibition of Activin/Nodal and Wnt signaling.

Bayramov AV , Eroshkin FM , Martynova NY , Ermakova GV , Solovieva EA , Zaraisky AG .


Abstract
The secreted protein Noggin1 is an embryonic inducer that can sequester TGFβ cytokines of the BMP family with extremely high affinity. Owing to this function, ectopic Noggin1 can induce formation of the headless secondary body axis in Xenopus embryos. Here, we show that Noggin1 and its homolog Noggin2 can also bind, albeit less effectively, to ActivinB, Nodal/Xnrs and XWnt8, inactivation of which, together with BMP, is essential for the head induction. In support of this, we show that both Noggin proteins, if ectopically produced in sufficient concentrations in Xenopus embryo, can induce a secondary head, including the forebrain. During normal development, however, Noggin1 mRNA is translated in the presumptive forebrain with low efficiency, which provides the sufficient protein concentration for only its BMP-antagonizing function. By contrast, Noggin2, which is produced in cells of the anterior margin of the neural plate at a higher concentration, also protects the developing forebrain from inhibition by ActivinB and XWnt8 signaling. Thus, besides revealing of novel functions of Noggin proteins, our findings demonstrate that specification of the forebrain requires isolation of its cells from BMP, Activin/Nodal and Wnt signaling not only during gastrulation but also at post-gastrulation stages.

PubMed ID: 22071106
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: admp bmp4 dkk1 foxg1 gsc hesx1 myc nodal nodal1 nodal2 nog nog2 odc1 pax6 tbxt wnt8a zyx
Morpholinos: bmp2 MO1 bmp4 MO1 bmp7.2 MO1 nog MO1 nog2 MO1


Article Images: [+] show captions