scholarly journals Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luca Guglielmi ◽  
Claire Heliot ◽  
Sunil Kumar ◽  
Yuriy Alexandrov ◽  
Ilaria Gori ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Embryo Development ◽  
Bmp Signaling ◽  
Nodal Signaling ◽  
Optical Projection Tomography ◽  
Core Component ◽  
Embryo Patterning ◽  
Optical Projection ◽  
Mesoderm Specification ◽  
Vertebrate Embryo

AbstractThe transcriptional effector SMAD4 is a core component of the TGF-β family signaling pathways. However, its role in vertebrate embryo development remains unresolved. To address this, we deleted Smad4 in zebrafish and investigated the consequences of this on signaling by the TGF-β family morphogens, BMPs and Nodal. We demonstrate that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling. However, unexpectedly, Nodal signaling is maintained, but lacks robustness. This Smad4-independent Nodal signaling is sufficient for mesoderm specification, but not for optimal endoderm specification. Furthermore, using Optical Projection Tomography in combination with 3D embryo morphometry, we have generated a BMP morphospace and demonstrate that Smad4 mutants are morphologically indistinguishable from embryos in which BMP signaling has been genetically/pharmacologically perturbed. Smad4 is thus differentially required for signaling by different TGF-β family ligands, which has implications for diseases where Smad4 is mutated or deleted.

scholarly journals Mechanism of CK2.3, a Novel Mimetic Peptide of Bone Morphogenetic Protein Receptor Type IA, Mediated Osteogenesis

2019 ◽  
Vol 20 (10) ◽  
pp. 2500 ◽  
Author(s):  
Vrathasha Vrathasha ◽  
Hilary Weidner ◽  
Anja Nohe
Keyword(s):  
Signaling Pathways ◽  
Treatment Options ◽  
Time Frame ◽  
Bmp Signaling ◽  
C2c12 Cells ◽  
Molecular Sequence ◽  
Sequence Of Events ◽  
Protein Receptor

Background: Osteoporosis is a degenerative skeletal disease with a limited number of treatment options. CK2.3, a novel peptide, may be a potential therapeutic. It induces osteogenesis and bone formation in vitro and in vivo by acting downstream of BMPRIA through releasing CK2 from the receptor. However, the detailed signaling pathways, the time frame of signaling, and genes activated remain largely unknown. Methods: Using a newly developed fluorescent CK2.3 analog, specific inhibitors for the BMP signaling pathways, Western blot, and RT-qPCR, we determined the mechanism of CK2.3 in C2C12 cells. We then confirmed the results in primary BMSCs. Results: Using these methods, we showed that CK2.3 stimulation activated OSX, ALP, and OCN. CK2.3 stimulation induced time dependent release of CK2β from BMPRIA and concurrently CK2.3 colocalized with CK2α. Furthermore, CK2.3 induced BMP signaling depends on ERK1/2 and Smad1/5/8 signaling pathways. Conclusion: CK2.3 is a novel peptide that drives osteogenesis, and we detailed the molecular sequence of events that are triggered from the stimulation of CK2.3 until the induction of mineralization. This knowledge can be applied in the development of future therapeutics for osteoporosis.

Time gated optical projection tomography for 3D imaging of highly scattering biological models

2010 ◽  
Author(s):  
Andrea Bassi ◽  
Daniele Brida ◽  
Cosimo D’Andrea ◽  
Gianluca Valentini ◽  
Sandro De Silvestri ◽  
...  
Keyword(s):  
3D Imaging ◽  
Optical Projection Tomography ◽  
Biological Models ◽  
Optical Projection

Optical Projection Tomography for Particle Counting and Morphology Analysis

2020 ◽  
pp. 944-951
Author(s):  
Olli Koskela ◽  
Md Tanvirul Kabir Chowdhury ◽  
Toni Montonen ◽  
Birhanu Belay ◽  
Sampsa Pursiainen ◽  
...  
Keyword(s):  
Optical Projection Tomography ◽  
Optical Projection ◽  
Particle Counting ◽  
Morphology Analysis

Distinct and cooperative roles for Nodal and Hedgehog signals during hypothalamic development

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3055-3065 ◽  
Author(s):  
Juliette Mathieu ◽  
Anukampa Barth ◽  
Frederic M. Rosa ◽  
Stephen W. Wilson ◽  
Nadine Peyriéras
Keyword(s):  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Evolutionary Conservation ◽  
Neural Plate ◽  
Nodal Signaling ◽  
Functional Importance ◽  
Anterior Dorsal ◽  
Site Of Action ◽  
Prechordal Plate ◽  
Further Development

Despite its evolutionary conservation and functional importance, little is known of the signaling pathways that underlie development of the hypothalamus. Although mutations affecting Nodal and Hedgehog signaling disrupt hypothalamic development, the time and site of action and the exact roles of these pathways remain very poorly understood. Unexpectedly, we show here that cell-autonomous reception of Nodal signals is neither required for the migration of hypothalamic precursors within the neural plate, nor for further development of the anterior-dorsal hypothalamus. Nodal signaling is, however, cell-autonomously required for establishment of the posterior-ventral hypothalamus. Conversely, Hedgehog signaling antagonizes the development of posterior-ventral hypothalamus, while promoting anterior-dorsal hypothalamic fates. Besides their distinct roles in the regionalization of the diencephalon, we reveal cooperation between Nodal and Hedgehog pathways in the maintenance of the anterior-dorsal hypothalamus. Finally we show that it is the prechordal plate and not the head endoderm that provides the early signals essential for establishment of the hypothalamus.

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