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Published on: July 21, 2021
Noggin1 and Follistatin-like2 function redundantly to Chordin to antagonize BMP activity
Sophie Dal-Pra1, Maximilian Fürthauer, Jeanne Van-Celst
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104, CNRS/INSERM/ULP, 1 rue Laurent Fries, BP 10142, CU de Strasbourg, 67404 ILLKIRCH Cedex, France.
Abstract:
In Xenopus, the dorso-ventral (D/V) axis is thought to be specified by the bone morphogenetic proteins (Bmp) activity arising through interaction with antagonists such as Noggin, Chordin and Follistatin. We report here, through inactivation of noggin1 (nog1) that this gene is not essential by itself to establish the D/V patterning. However, at blastula stage, inactivation of nog1 strongly amplifies chordin (chd) phenotype, revealing redundant functions of these two genes on D/V axis formation. Substantial dorsal tissues remaining in the double nog1-chd morphant suggested that other anti-Bmp factors may pattern the D/V axis. We isolated two potential candidates, the follistatin-like (fstl) genes. We found that fstl2 is an early gastrula expressed gene. Its inactivation, similar to nog1, strongly enhances the chd phenotype. Moreover, the penetrance of the ventralization phenotype is much higher when we inactivated simultaneously chd, nog1 and fstl2. Altogether, our data reveal that, while Chordin is the main player of the D/V axis, sufficient to maintain proper activity of Bmp gradient, the structures remaining in the chd mutant (namely dorsal and dorso-lateral territories, in both mesodermal and ectodermal layers) result from the anti-Bmp activity carried by Nog1 and Fstl2 at blastula and gastrula stages.
Insights
In Xenopus, Chordin is the primary factor for dorso-ventral axis patterning. However, Noggin1 and Follistatin-like 2 provide redundant anti-BMP activity, crucial for complete axis formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- The dorso-ventral (D/V) axis in Xenopus is established by bone morphogenetic protein (Bmp) signaling.
- Antagonists like Noggin, Chordin, and Follistatin modulate Bmp activity to specify the D/V axis.
Purpose of the Study:
- To investigate the individual and combined roles of noggin1 (nog1), chordin (chd), and follistatin-like 2 (fstl2) in Xenopus D/V axis patterning.
- To identify the key anti-Bmp factors responsible for D/V axis formation.
Main Methods:
- Gene inactivation via morpholino-based knockdown of nog1, chd, and fstl2 in Xenopus embryos.
- Phenotypic analysis of D/V axis patterning in single and multiple gene knockdowns.
Main Results:
- Inactivation of nog1 alone does not disrupt D/V patterning but significantly enhances the chordin (chd) phenotype, indicating functional redundancy.
- Follistatin-like 2 (fstl2) is expressed during early gastrulation and its inactivation also enhances the chd phenotype.
- Simultaneous inactivation of chd, nog1, and fstl2 results in a high penetrance of the ventralization phenotype, suggesting a combined role.
Conclusions:
- Chordin is the principal antagonist regulating the Bmp gradient for D/V axis specification.
- Noggin1 and Fstl2 exhibit redundant anti-Bmp activities, contributing to the formation of dorsal and dorso-lateral tissues, particularly at blastula and gastrula stages.
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