A Smad3 transgenic reporter reveals TGF-beta control of zebrafish spinal cord development

Casari, Alessandro; Schiavone, Marco; Facchinello, Nicola; Vettori, Andrea; Meyer, Dirk; Tiso, Natascia; Moro, Enrico; Argenton, Francesco

doi:10.1016/j.ydbio.2014.09.025

Cited by 59 publications

(52 citation statements)

References 47 publications

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“…SB431542 is a well-characterized inhibitor of the TGF-β family receptor kinases Alk4/5 [61], that is also known to inhibit TGF-β signaling activity in the zebrafish [62–64]. To avoid perturbing earlier developmental roles of TGF-β family signaling, embryos were treated with 10μM SB431542 starting at the 14- to 15-somites stages.…”

Section: Resultsmentioning

confidence: 99%

Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development

et al. 2016

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Birth defects are among the leading causes of infant mortality and contribute substantially to illness and long-term disability. Defects in Bone Morphogenetic Protein (BMP) signaling are associated with cleft lip/palate. Many craniofacial syndromes are caused by defects in signaling pathways that pattern the cranial neural crest cells (CNCCs) along the dorsal-ventral axis. For example, auriculocondylar syndrome is caused by impaired Endothelin-1 (Edn1) signaling, and Alagille syndrome is caused by defects in Jagged-Notch signaling. The BMP, Edn1, and Jag1b pathways intersect because BMP signaling is required for ventral edn1 expression that, in turn, restricts jag1b to dorsal CNCC territory. In zebrafish, the scaffolding protein Wdr68 is required for edn1 expression and subsequent formation of the ventral Meckel’s cartilage as well as the dorsal Palatoquadrate. Here we report that wdr68 activity is required between the 17-somites and prim-5 stages, that edn1 functions downstream of wdr68, and that wdr68 activity restricts jag1b, hey1, and grem2 expression from ventral CNCC territory. Expression of dlx1a and dlx2a was also severely reduced in anterior dorsal and ventral 1st arch CNCC territory in wdr68 mutants. We also found that the BMP agonist isoliquiritigenin (ISL) can partially rescue lower jaw formation and edn1 expression in wdr68 mutants. However, we found no significant defects in BMP reporter induction or pSmad1/5 accumulation in wdr68 mutant cells or zebrafish. The Transforming Growth Factor Beta (TGF-β) signaling pathway is also known to be important for craniofacial development and can interfere with BMP signaling. Here we further report that TGF-β interference with BMP signaling was greater in wdr68 mutant cells relative to control cells. To determine whether interference might also act in vivo, we treated wdr68 mutant zebrafish embryos with the TGF-β signaling inhibitor SB431542 and found partial rescue of edn1 expression and craniofacial development. While ISL treatment failed, SB431542 partially rescued dlx2a expression in wdr68 mutants. Together these findings reveal an indirect role for Wdr68 in the BMP-Edn1-Jag1b signaling hierarchy and dorso-anterior expression of dlx1a/2a.

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Section: Resultsmentioning

confidence: 99%

Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development

et al. 2016

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“…SMAD3 is a key signaling protein in the TGF-β1 signaling pathway (30). Following its transcription, the phosphorylation of various proteins determines the functions of the TGF-β1 signaling pathway (31).…”

Section: Discussionmentioning

confidence: 99%

Deregulation of miR-193b affects the growth of colon cancer cells via transforming growth factor-β and regulation of the SMAD3 pathway

Zhao

et al. 2017

Oncology Letters

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MicroRNA-193b (miRNA-193b) is often differentially expressed and is an important regulator of gene expression in colon cancer. The aim of the present study was to determine whether miRNA-193b affects cell growth in colon cancer and to investigate the potential underlying mechanisms. Patients with colorectal cancer (CRC; n=20) and healthy volunteers (n=10) were enrolled from the Department of Gastrointestinal Surgery Center, First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China). Western blot analysis was used to evaluate the protein expression of SMAD3 and transforming growth factor-β (TGF-β) in the patient samples. It was determined that miRNA-193b expression was markedly elevated in the CRC tissue samples. Furthermore, silencing of miRNA-193bin SW620 CRC cells by specific inhibitors significantly reduced the cell proliferation and induced apoptosis. In addition, the downregulation of miRNA-193b significantly activated the protein expression of SMAD3 and TGF-β, and promoted caspase-3 activity in SW620 cells. The results of the present study suggested that the deregulation of miRNA-193b may affect cell growth in colon cancer via the TGF-β and SMAD3 signaling pathways.

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“…SMAD3 which was shown to promote neuronal differentiation in spinal cord of zebrafish [60] was found to be higher expressed in patterned MNs compared to iN cells. In addition, several TFs are upregulated at early time points of neuronal differentiation.…”

Section: Transcription Factors and Cytoskeletal Proteinsmentioning

confidence: 93%

Deciphering the protein dynamics and molecular determinants of iPSC-derived neurons

Varderidou-Minasian

Schätzle

et al. 2019

Preprint

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Neuronal development is a multistep process with different regulatory programs that shapes neurons to form dendrites, axons and synapses. To date, knowledge on neuronal development is largely based on murine data and largely restricted to the genomic and transcriptomic level. Advances in stem cell differentiation now enable the study of human neuronal development, and here we provide a mass spectrometry-based quantitative proteomic signature, at high temporal resolution, of human stem cellderived neurons. To reveal proteomic changes during neuronal development we make use of two differentiation approaches, either by expression of neurogenin-2 (Ngn2) leading to glutamatergic induced neurons (iN) or via small molecule manipulations, leading to patterned motor neurons. Our analysis revealed key proteins that show significant expression changes (FDR <0.001) during neuronal differentiation. We overlay our proteomics data with available transcriptomic data during neuronal differentiation and show distinct, datatype-specific, signatures. Overall, we provide a rich resource of information on proteins associated with human neuronal development, and moreover, highlight several signaling pathways involved, such as Wnt and Notch. 2 KEYWORDS iPSC; human; neuron differentiation; quantitative mass spectrometry; TMT-10plex

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A Smad3 transgenic reporter reveals TGF-beta control of zebrafish spinal cord development

Cited by 59 publications

References 47 publications

Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development

Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development

Deregulation of miR-193b affects the growth of colon cancer cells via transforming growth factor-β and regulation of the SMAD3 pathway

Deciphering the protein dynamics and molecular determinants of iPSC-derived neurons

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