Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development

Vieira, José Ricardo dos Santos; Shah, Bhavin; Dupraz, Sebastián; Paredes, Isidora; Himmels, Patricia; Schermann, Géza; Adler, Heike; Motta, Alessia; Gärtner, Lea; Navarro-Aragall, Ariadna Gador; Ioannou, Elena; Dyukova, Elena; Bonnavion, Rémy; Fischer, Andreas; Bonanomi, Dario; Bradke, Frank; Ruhrberg, Christiana; Almodóvar, Carmen Ruiz de

doi:10.1016/j.neuron.2022.12.005

Cited by 9 publications

(5 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another plexin receptor, Plexin D1, has been reported to be involved in the regulation of ChAT expression in motor neurons. 35 Whether Sema5A/Plexin A2 interaction might also regulate ChAT expression and, therefore, impact on cholinergic neurotransmission remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

The regulation of enteric neuron connectivity by semaphorin 5A is affected by the autism-associated S956G missense mutation

Le Dréan,

Le Berre-Scoul,

Paillé

et al. 2024

iScience

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

The regulation of enteric neuron connectivity by semaphorin 5A is affected by the autism-associated S956G missense mutation

Le Dréan,

Le Berre-Scoul,

Paillé

et al. 2024

iScience

View full text Add to dashboard Cite

“…Since MMP-9 plays a critical role in the angiogenic switch during carcinogenesis, its inhibition by NDRG1 and NDRG2expression is likely correlated with decreased angiogenesis. SEMA3C function is related to the development of spinal cord blood vessels in neuronal cells [ 37 ] and promotes angiogenesis in vascular epithelial cells [ 38 ]. Among the downregulated heart-related DEGs, G protein-coupled estrogen receptor 1 (GPER1) is associated with neuronal survival [ 39 ] and mediates protection within the cardiovascular and renal systems [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

SGK1 Target Genes Involved in Heart and Blood Vessel Functions in PC12 Cells

Sun

Chen

et al. 2023

Cells

View full text Add to dashboard Cite

Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases.

show abstract

“…While we did not observe heterogeneity in EC proliferation, the higher abundance of tip cells in the THAL compared to CTX suggests that tip cell-mediated vascular remodeling could be responsible for the observed vascular heterogeneity. A recent study has shown that regional vascular density affects neuronal function in the mouse developing spinal cord 44 . The role of blood vessels in neuronal identity and activity of developing THAL remains unknown and will require further investigation.…”

Section: Discussionmentioning

confidence: 99%

A molecular atlas of brain neurovascular interactions reveals a spatiotemporal requirement of TGFβ signaling in brain angiogenesis

Dubrac,

Bizou,

Howard

et al. 2023

Preprint

View full text Add to dashboard Cite

Neurovascular interactions (NVIs) are critical in establishing vascular patterning, barrier function, and in regulating cerebral blood flow, thereby maintaining neuronal homeostasis and brain health. While developmental programs and neuronal activity play a central role in cerebral cortex angiogenesis during a critical postnatal period, whether cellular heterogeneity causes region-specific angiogenic regulation remains unknown. Here, we combine spatial and endothelial single-cell RNAseq (scRNAseq) transcriptomic analysis to establish a molecular atlas of developing brain regions and a comprehensive list of spatiotemporal-specific NVIs. We find that the thalamic area has a higher vascular density than the other brain regions and our atlas identifies transforming growth factor β (Tgfβ) and Vegfc ligands enrichment in this area during a critical postnatal period. Neonatal endothelial Tgfβr1 deletion (Tgfβr1iEKO) induces vascular malformations and hemorrhages, primarily in the thalamic area. Mechanistically, we show that loss of endothelial TGFβ signaling increases VEGFC-induced AKT/mTOR signaling in vitro and in vivo, and that mTOR inhibitor Rapamycin efficiently inhibits intracerebral bleeding and vascular defects in Tgfβr1iEKO mice. Altogether, our data suggest that spatiotemporal-specific NVIs control brain vascular heterogeneity, which extends our knowledge of region-specific cerebrovascular development and will benefit our understanding of neurovascular disorders.

show abstract

Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development

Cited by 9 publications

References 76 publications

The regulation of enteric neuron connectivity by semaphorin 5A is affected by the autism-associated S956G missense mutation

The regulation of enteric neuron connectivity by semaphorin 5A is affected by the autism-associated S956G missense mutation

SGK1 Target Genes Involved in Heart and Blood Vessel Functions in PC12 Cells

A molecular atlas of brain neurovascular interactions reveals a spatiotemporal requirement of TGFβ signaling in brain angiogenesis

Contact Info

Product

Resources

About