Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5

Maerker, Markus; Getwan, Maike; Dowdle, Megan E.; McSheene, Jason C.; Gonzalez, Vanessa; Pelliccia, José L; Hamilton, Danielle S; Yartseva, Valeria; Vejnar, Charles E.; Tingler, Melanie; Minegishi, Katsura; Vick, Philipp; Giráldez, Antonio J.; Hamada, Hiroshi; Burdine, Rebecca D.; Sheets, Michael; Blum, Martin; Schweickert, Axel

doi:10.1038/s41467-021-25464-z

Cited by 31 publications

(32 citation statements)

References 67 publications

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“…Among the validated targets were mRNAs such as cripto1 and dand5 that encode known signaling proteins important for fate decisions in Xenopus and other vertebrate embryos ( Tao et al, 2005 ; Bates et al, 2013 ). Subsequent studies in Xenopus also identified the wnt11b and gdf3 mRNAs as additional authentic Bicc1 targets ( Park et al, 2016 ; Maerker et al, 2021 ). These results defined the Bicc1 target mRNA network and provided a foundation for understanding the molecular events that underlie Bicc1 regulated biological events during vertebrate development and potentially other contexts.…”

Section: Bicaudal-c Target Mrnasmentioning

confidence: 97%

“…Heterotaxy is the abnormal arrangement and structure of the abdominal organs, especially the heart. Recent evidence suggests that L-R defects due to Bicc1 are at least in part due to disrupted Bicc1 regulation of the mRNA encoding the Nodal inhibitor dand5 ( Maerker et al, 2021 ; Minegishi et al, 2021 ). The results from these studies demonstrated the central role of Bicc1 RNA regulation in controlling L-R patterning.…”

Section: Bicaudal-c Regulated Biological Processesmentioning

confidence: 99%

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Bicaudal-C Post-transcriptional regulator of cell fates and functions

Dowdle

Kanzler²,

Harder³

et al. 2022

Front. Cell Dev. Biol.

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Bicaudal-C (Bicc1) is an evolutionarily conserved RNA binding protein that functions in a regulatory capacity in a variety of contexts. It was originally identified as a genetic locus in Drosophila that when disrupted resulted in radical changes in early development. In the most extreme phenotypes embryos carrying mutations developed with mirror image duplications of posterior structures and it was this striking phenotype that was responsible for the name Bicaudal. These seminal studies established Bicc1 as an important regulator of Drosophila development. What was not anticipated from the early work, but was revealed subsequently in many different organisms was the broad fundamental impact that Bicc1 proteins have on developmental biology; from regulating cell fates in vertebrate embryos to defects associated with several human disease states. In the following review we present a perspective of Bicc1 focusing primarily on the molecular aspects of its RNA metabolism functions in vertebrate embryos.

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Section: Bicaudal-c Target Mrnasmentioning

confidence: 97%

Section: Bicaudal-c Regulated Biological Processesmentioning

confidence: 99%

Bicaudal-C Post-transcriptional regulator of cell fates and functions

Dowdle

Kanzler²,

Harder³

et al. 2022

Front. Cell Dev. Biol.

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“…Recently, we and others demonstrated that Dand5 reduction is due to the inhibition of dand5 mRNA translation and its subsequent decay. In these studies, the RNA binding protein Bicaudal C1 was identified as the post-transcriptional mediator of flow-induced signaling leading to dand5 mRNA repression ( Maerker et al, 2021 ; Minegishi et al, 2021 ). Upon Dand5 reduction, Nodal is released from sLRO cells and conveys left positional information to the left lateral plate mesoderm (LPM).…”

Section: Introductionmentioning

confidence: 99%

dmrt2 and myf5 Link Early Somitogenesis to Left-Right Axis Determination in Xenopus laevis

Tingler

Brugger

Feistel

et al. 2022

Front. Cell Dev. Biol.

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The vertebrate left-right axis is specified during neurulation by events occurring in a transient ciliated epithelium termed left-right organizer (LRO), which is made up of two distinct cell types. In the axial midline, central LRO (cLRO) cells project motile monocilia and generate a leftward fluid flow, which represents the mechanism of symmetry breakage. This directional fluid flow is perceived by laterally positioned sensory LRO (sLRO) cells, which harbor non-motile cilia. In sLRO cells on the left side, flow-induced signaling triggers post-transcriptional repression of the multi-pathway antagonist dand5. Subsequently, the co-expressed Tgf-β growth factor Nodal1 is released from Dand5-mediated repression to induce left-sided gene expression. Interestingly, Xenopus sLRO cells have somitic fate, suggesting a connection between LR determination and somitogenesis. Here, we show that doublesex and mab3-related transcription factor 2 (Dmrt2), known to be involved in vertebrate somitogenesis, is required for LRO ciliogenesis and sLRO specification. In dmrt2 morphants, misexpression of the myogenic transcription factors tbx6 and myf5 at early gastrula stages preceded the misspecification of sLRO cells at neurula stages. myf5 morphant tadpoles also showed LR defects due to a failure of sLRO development. The gain of myf5 function reintroduced sLRO cells in dmrt2 morphants, demonstrating that paraxial patterning and somitogenesis are functionally linked to LR axis formation in Xenopus.

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“…BICC1 is a multicellular animal evolutionarily conserved RNA binding protein that plays a vital role in signal transduction pathways, organ development, and homeostasis [ 6 ]. At least three Biccl mutant mice (jcpk, bpk, and 67Gso) have been reported.…”

Section: Introductionmentioning

confidence: 99%

Expression and Regulatory Network Analysis of BICC1 for Aged Sca-1-Positive Bone Narrow Mesenchymal Stem Cells

Liu

Xiang

et al. 2022

Disease Markers

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Background. The impaired osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a major cause of bone remodeling imbalance and osteoporosis. The bicaudal C homologue 1 (BICC1) gene is a genetic regulator of bone mineral density (BMD) and promotes osteoblast differentiation. The purpose of this study is to explore the probable function of BICC1 in osteoporosis and osteogenic differentiation of aged BMSCs. Methods. We examined the GSE116925 microarray dataset obtained from the Gene Expression Omnibus (GEO) database. The GEO2R algorithm identified differentially expressed genes (DEGs) in Sca-1+ BMSCs from young (3 months old) and old (18 months old) mice. Then, to identify the most crucial genes, we used pathway enrichment analysis and a protein-protein interaction (PPI) network. Furthermore, starBase v2.0 was used to generate the regulatory networks between BICC1 and related competing endogenous RNAs (ceRNAs). NetworkAnalyst was used to construct TF-gene networks and TF-miRNA-gene networks of BICC1 and ceRNA. Furthermore, we investigated the Bicc1 expression in aged Sca-1-positive BMSCs. Result. We detected 923 DEGs and discovered that epidermal growth factor receptor (EGFR) was the top hub gene with a high degree of linkage. According to the findings of the PPI module analysis, EGFR was mostly engaged in cytokine signaling in immune system and inflammation-related signaling pathways. 282 ceRNAs were found to interact with the BICC1 gene. EGFR was not only identified as a hub gene but also as a BICC1-related ceRNA. Then, we predicted 11 common TF-genes and 7 miRNAs between BICC1 and EGFR. Finally, we found that BICC1 mRNA and EGFR mRNA were significantly overexpressed in aged Sca-1-positive BMSCs. Conclusion. As a genetic gene that affects bone mineral density, BICC1 may be a new target for clinical treatment of senile osteoporosis by influencing osteogenic differentiation of BMSCs through EGFR-related signaling. However, the application of the results requires support from more experimental data.

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Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5

Cited by 31 publications

References 67 publications

Bicaudal-C Post-transcriptional regulator of cell fates and functions

Bicaudal-C Post-transcriptional regulator of cell fates and functions

dmrt2 and myf5 Link Early Somitogenesis to Left-Right Axis Determination in Xenopus laevis

Expression and Regulatory Network Analysis of BICC1 for Aged Sca-1-Positive Bone Narrow Mesenchymal Stem Cells

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