BMP2 induction of actin cytoskeleton reorganization and cell migration requires PI3-kinase and Cdc42 activity

Gamell, Cristina; Osses, Nelson; Bartrons, Ramón; Rückle, Thomas; Camps, Montserrat; Rosa, José Luís; Ventura, Francesc

doi:10.1242/jcs.031286

Cited by 109 publications

(123 citation statements)

References 62 publications

(86 reference statements)

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“…For example, it has been shown that BMP2 enhances the motility of prostate cancer cells via activation of integrins (30) and affects actin cytoskeleton reorganization and cell migration through regulation of phosphatidylinositide 3-kinase and cell division control protein 42 activity (40). Effects on LIM kinase 1 (LIMK), a key regulator of actin dynamics, which phosphorylates and inactivates cofilin, an actin depolymerizing factor, have also been reported (41,42).…”

Section: Discussionmentioning

confidence: 99%

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Song

McColl

Camp

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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In vertebrate embryos, cardiac progenitor cells (CPCs) undergo long-range migration after emerging from the primitive streak during gastrulation. Together with other mesoderm progenitors, they migrate laterally and then toward the ventral midline, where they form the heart. Signals controlling the migration of different progenitor cell populations during gastrulation are poorly understood. Several pathways are involved in the epithelialto-mesenchymal transition and ingression of mesoderm cells through the primitive streak, including fibroblast growth factors and wingless-type family members (Wnt). Here we focus on early CPC migration and use live video microscopy in chicken embryos to demonstrate a role for bone morphogenetic protein (BMP)/SMA and MAD related (Smad) signaling. We identify an interaction of BMP and Wnt/glycogen synthase kinase 3 beta (GSK3β) pathways via the differential phosphorylation of Smad1. Increased BMP2 activity altered migration trajectories of prospective cardiac cells and resulted in their lateral displacement and ectopic differentiation, as they failed to reach the ventral midline. Constitutively active BMP receptors or constitutively active Smad1 mimicked this phenotype, suggesting a cell autonomous response. Expression of GSK3β, which promotes the turnover of active Smad1, rescued the BMP-induced migration phenotype. Conversely, expression of GSK3β-resistant Smad1 resulted in aberrant CPC migration trajectories. Derepression of GSK3β by dominant negative Wnt3a restored normal migration patterns in the presence of high BMP activity. The data indicate the convergence of BMP and Wnt pathways on Smad1 during the early migration of prospective cardiac cells. Overall, we reveal molecular mechanisms that contribute to the emerging paradigm of signaling pathway integration in embryo development.live imaging | cell tracking

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Section: Discussionmentioning

confidence: 99%

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Song

McColl

Camp

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Two additional SMADs are known as inhibitory SMADs, SMAD6 and SMAD7. Furthermore, BMPs can also activate noncanonical, SMAD-independent pathways, mainly MAPK pathways (Erk, p38), the LIMK pathway, or the PI3K pathway, which are also involved in osteoblast differentiation (Shi & Massague 2003, Gamell et al 2008, Ulsamer et al 2008, Ortuno et al 2010.…”

Section: The Interplay Between Mirnas and Bmp Signalingmentioning

confidence: 99%

MicroRNAs and post-transcriptional regulation of skeletal development

Gámez¹,

Rodríguez-Carballo²,

Ventura³

2014

Journal of Molecular Endocrinology

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MicroRNAs (miRNAs) have become integral nodes of post-transcriptional control of genes that confer cellular identity and regulate differentiation. Cell-specific signaling and transcriptional regulation in skeletal biology are extremely dynamic processes that are highly reliant on dose-dependent responses. As such, skeletal cell-determining genes are ideal targets for quantitative regulation by miRNAs. So far, large amounts of evidence have revealed a characteristic temporal miRNA signature in skeletal cell differentiation and confirmed the essential roles that numerous miRNAs play in bone development and homeostasis. In addition, microarray expression data have provided evidence for their role in several skeletal pathologies. Mouse models in which their expression is altered have provided evidence of causal links between miRNAs and bone abnormalities. Thus, a detailed understanding of the function of miRNAs and their tight relationship with bone diseases would constitute a powerful tool for early diagnosis and future therapeutic approaches.

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“…Sotobori et al (2006) suggested that BMP-2 promotes the migration of osteosarcoma cells through fibronectin-integrin β1 signaling, and Lai et al (2008) reported that BMP-2 promotes the migration of prostate cancer cells by activating integrins β1 and β3. Recently, Gamell et al (2008) proposed that BMP-2 influences the reorganization of the cytoskeleton by activating PI3K and Cdc42 of the Rho GTPase superfamily and its downstream molecules (PAK1, LIMK1, etc. ), so as to regulate cell migration further.…”

Section: Discussionmentioning

confidence: 99%

Construction of a eukaryotic expression vector pEGFP-C1-BMP-2 and its effect on cell migration

Wang

Chen

Zhang

et al. 2012

J. Zhejiang Univ. Sci. B

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Abstract:Objective: Bone morphogenetic proteins (BMPs) are known to play an important role in bone and cartilage development. Recent research has shown that BMPs may induce tumorigenesis and promote tumor to spread, but the molecular mechanisms have not been elucidated. The aim of the present study was to investigate the regulatory function of BMP-2 in the migration of COS-7 cells and the underlying mechanisms. Methods: Human BMP-2 genetic fragment was amplified and introduced into the pEGFP-C1 vector. After being confirmed by XhoI and BamHI digestion analyses and DNA sequencing, the recombinant pEGFP-C1-BMP-2 plasmid was transfected into COS-7 cells. The influence of BMP-2 on cell migration and cofilin activity was detected by cell scratch assay and Western blotting. Results: The recombinant pEGFP-C1-BMP-2 was effectively expressed in COS-7 cells. An increased phosphorylation of both LIMK1 and cofilin and an enhancement of cell migration were observed in cells with overexpression of BMP-2. Conclusions: A recombinant pEGFP-C1-BMP-2 vector was successfully constructed and overexpression of BMP-2 regulated the activities of the downstream molecules of the Rho GTPase signaling pathway, which might contribute to the enhancement of cell migration.

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BMP2 induction of actin cytoskeleton reorganization and cell migration requires PI3-kinase and Cdc42 activity

Cited by 109 publications

References 62 publications

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

MicroRNAs and post-transcriptional regulation of skeletal development

Construction of a eukaryotic expression vector pEGFP-C1-BMP-2 and its effect on cell migration

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