Similar Datasets
Project description:The canonical bone morphogenetic protein (BMP) signaling pathway plays a crucial regulatory role in tooth development by activating Smad proteins to regulate gene expression. We previously identified an atypical canonical BMP signaling in dental mesenchyme that is Smad4-independent but Smad1/5-dependent. This study demonstrates that phosphorylated Smad1/5 (pSmad1/5) and Smad4 regulate distinct gene sets in dental mesenchyme. Real-time monitoring of BMP-Smad transcriptional activity revealed that Smad4-dependent canonical BMP signaling is restricted to neurovascular cells surrounding the condensed dental mesenchymal cells where pSmad1/5 is present. Notably, pSmad1/5 in dental mesenchymal cells form complexes with pSmad3 to prevent canonical BMP signaling. CUT&RUN assays revealed genome-wide co-occupancy of pSmad1/5 and pSmad3, indicating their function as transcriptional regulation units. Integrative analyses demonstrated that this atypical canonical BMP signaling regulates tooth sensory innervation and maintains odontogenic inductive potential in dental mesenchyme, enabling the identification of critical genes for maintaining tooth inductive capability. Our findings elucidate the operating mechanism of atypical canonical BMP signaling in dental mesenchymal cells and clarify how BMP-Smad signaling exerts diverse functions across different cell types, informing future tooth bioengineering strategies.
2025-06-05 | GSE297137 | GEO
Project description:The canonical bone morphogenetic protein (BMP) signaling pathway plays a crucial regulatory role in tooth development by activating Smad proteins to regulate gene expression. We previously identified an atypical canonical BMP signaling in dental mesenchyme that is Smad4-independent but Smad1/5-dependent. This study demonstrates that phosphorylated Smad1/5 (pSmad1/5) and Smad4 regulate distinct gene sets in dental mesenchyme. Real-time monitoring of BMP-Smad transcriptional activity revealed that Smad4-dependent canonical BMP signaling is restricted to neurovascular cells surrounding the condensed dental mesenchymal cells where pSmad1/5 is present. Notably, pSmad1/5 in dental mesenchymal cells form complexes with pSmad3 to prevent canonical BMP signaling. CUT&RUN assays revealed genome-wide co-occupancy of pSmad1/5 and pSmad3, indicating their function as transcriptional regulation units. Integrative analyses demonstrated that this atypical canonical BMP signaling regulates tooth sensory innervation and maintains odontogenic inductive potential in dental mesenchyme, enabling the identification of critical genes for maintaining tooth inductive capability. Our findings elucidate the operating mechanism of atypical canonical BMP signaling in dental mesenchymal cells and clarify how BMP-Smad signaling exerts diverse functions across different cell types, informing future tooth bioengineering strategies.
2025-06-05 | GSE297033 | GEO
Project description:The canonical bone morphogenetic protein (BMP) signaling pathway plays a crucial regulatory role in tooth development by activating Smad proteins to regulate gene expression. We previously identified an atypical canonical BMP signaling in dental mesenchyme that is Smad4-independent but Smad1/5-dependent. This study demonstrates that phosphorylated Smad1/5 (pSmad1/5) and Smad4 regulate distinct gene sets in dental mesenchyme. Real-time monitoring of BMP-Smad transcriptional activity revealed that Smad4-dependent canonical BMP signaling is restricted to neurovascular cells surrounding the condensed dental mesenchymal cells where pSmad1/5 is present. Notably, pSmad1/5 in dental mesenchymal cells form complexes with pSmad3 to prevent canonical BMP signaling. CUT&RUN assays revealed genome-wide co-occupancy of pSmad1/5 and pSmad3, indicating their function as transcriptional regulation units. Integrative analyses demonstrated that this atypical canonical BMP signaling regulates tooth sensory innervation and maintains odontogenic inductive potential in dental mesenchyme, enabling the identification of critical genes for maintaining tooth inductive capability. Our findings elucidate the operating mechanism of atypical canonical BMP signaling in dental mesenchymal cells and clarify how BMP-Smad signaling exerts diverse functions across different cell types, informing future tooth bioengineering strategies.
2025-06-05 | GSE296697 | GEO
Project description:Distinct BMP-Smad Signaling Outputs Confer Diverse Functions in Dental Mesenchyme
| PRJNA1262859 | ENA
Project description:Distinct BMP-Smad Signaling Outputs Confer Diverse Functions in Dental Mesenchyme [CUT&Run]
| PRJNA1262426 | ENA
Project description:Distinct BMP-Smad Signaling Outputs Confer Diverse Functions in Dental Mesenchyme [RNA-seq]
| PRJNA1262861 | ENA
Project description:Distinct BMP-Smad Signaling Outputs Confer Diverse Functions in Dental Mesenchyme [ChIP-seq]
| PRJNA1260552 | ENA
Project description:Bone Morphogenetic Proteins (BMPs) have multiple activities in the developing spinal cord: they specify the identity of the dorsal-most neuronal populations and then direct the trajectories of dorsal interneuron (dI) 1 commissural axons. How are these activities decoded by dorsal neurons to result in different cellular outcomes? Our previous studies have shown that the diverse functions of the BMPs are mediated by the canonical family of BMP receptors and then regulated by specific inhibitory (I) Smads, which block the activity of a complex of Smad second messengers. However, the extent to which this complex translates the different activities of the BMPs in the spinal cord has remained unresolved. Here, we demonstrate that the receptor-activated (R) Smads, Smad1 and Smad5 play distinct roles mediating the abilities of the BMPs to direct cell fate specification and axon outgrowth. Smad1 and Smad5 occupy spatially distinct compartments within the spinal cord, with Smad5 primarily associated with neural progenitors and Smad1 with differentiated neurons. Consistent with this expression profile, loss of function experiments in mouse embryos reveal that Smad5 is required for the acquisition of dorsal spinal neuron identities whereas Smad1 is critical for the regulation of dI1 axon outgrowth. Thus the R-Smads, like the I-Smads, have discrete roles mediating BMP-dependent cellular processes during spinal interneuron development.
| S-EPMC3380454 | biostudies-literature
Project description:Kinase activation and substrate phosphorylation commonly form the backbone of signaling cascades. Bone morphogenetic proteins (BMPs), a subclass of TGF-β family ligands, induce activation of their signaling effectors, the Smads, through C-terminal phosphorylation by transmembrane receptor kinases. However, the slow kinetics of Smad activation in response to BMP suggests a preceding step in the initiation of BMP signaling. We now show that arginine methylation, which is known to regulate gene expression, yet also modifies some signaling mediators, initiates BMP-induced Smad signaling. BMP-induced receptor complex formation promotes interaction of the methyltransferase PRMT1 with the inhibitory Smad6, resulting in Smad6 methylation and relocalization at the receptor, leading to activation of effector Smads through phosphorylation. PRMT1 is required for BMP-induced biological responses across species, as evidenced by the role of its ortholog Dart1 in BMP signaling during Drosophila wing development. Activation of signaling by arginine methylation may also apply to other signaling pathways.
| S-EPMC3951972 | biostudies-literature
Project description:Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible allele of a BMP inhibitor, Gremlin, which reduces BMP signaling. We show that BMPs act in a dose and time dependent manner in which early reduction of BMPs result in digit loss, while inhibiting overall BMP signaling between E10.5 and E11.5 allows polydactylous digit formation. During this period, inhibiting BMPs extends the duration of FGF signaling. Sox9 is initially expressed in normal digit ray domains but at reduced levels that correlate with the reduction in BMP signaling. The persistence of elevated FGF signaling likely promotes cell proliferation and survival, inhibiting the activation of Sox9 and secondarily, inhibiting the differentiation of Sox9-expressing chondrocytes. Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis.
| S-EPMC4143117 | biostudies-literature