scholarly journals Resolving in vivo gene expression during collective cell migration using an integrated RNAscope, immunohistochemistry and tissue clearing method

2017 ◽  
Vol 148 ◽  
pp. 100-106 ◽  
Author(s):  
Jason A. Morrison ◽  
Mary Cathleen McKinney ◽  
Paul M. Kulesa
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Collective Cell Migration ◽  
Tissue Clearing ◽  
Clearing Method

scholarly journals Self-organized cell migration across scales – from single cell movement to tissue formation

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
pp. dev191767
Author(s):  
Jessica Stock ◽  
Andrea Pauli
Keyword(s):  
Cell Migration ◽  
Multiple Scales ◽  
Single Cells ◽  
Cell Movement ◽  
Biological Response ◽  
Collective Cell Migration ◽  
Theoretical Concepts ◽  
Self Organizing

ABSTRACTSelf-organization is a key feature of many biological and developmental processes, including cell migration. Although cell migration has traditionally been viewed as a biological response to extrinsic signals, advances within the past two decades have highlighted the importance of intrinsic self-organizing properties to direct cell migration on multiple scales. In this Review, we will explore self-organizing mechanisms that lay the foundation for both single and collective cell migration. Based on in vitro and in vivo examples, we will discuss theoretical concepts that underlie the persistent migration of single cells in the absence of directional guidance cues, and the formation of an autonomous cell collective that drives coordinated migration. Finally, we highlight the general implications of self-organizing principles guiding cell migration for biological and medical research.

Abstract 4306: Lack of TGF-β signaling induces a switch from single to collective cell migration in vivo

2012 ◽  
Author(s):  
Lauren A. Matise ◽  
Trenis D. Palmer ◽  
William J. Ashby ◽  
Abudi Nashabi ◽  
Anna Chytil ◽  
...  
Keyword(s):  
Cell Migration ◽  
Collective Cell Migration

scholarly journals α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways

2021 ◽  
Vol 9 ◽  
Author(s):  
Willow Hight-Warburton ◽  
Robert Felix ◽  
Andrew Burton ◽  
Hannah Maple ◽  
Magda S. Chegkazi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Complexes ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Collective Cell Migration ◽  
Keratinocyte Proliferation ◽  
Basal Keratinocytes ◽  
Keratinocyte Cell

Adhesion of basal keratinocytes to the underlying extracellular matrix (ECM) plays a key role in the control of skin homeostasis and response to injury. Integrin receptors indirectly link the ECM to the cell cytoskeleton through large protein complexes called focal adhesions (FA). FA also function as intracellular biochemical signaling platforms to enable cells to respond to changing extracellular cues. The α4β1 and α9β1 integrins are both expressed in basal keratinocytes, share some common ECM ligands, and have been shown to promote wound healing in vitro and in vivo. However, their roles in maintaining epidermal homeostasis and relative contributions to pathological processes in the skin remain unclear. We found that α4β1 and α9β1 occupied distinct regions in monolayers of a basal keratinocyte cell line (NEB-1). During collective cell migration (CCM), α4 and α9 integrins co-localized along the leading edge. Pharmacological inhibition of α4β1 and α9β1 integrins increased keratinocyte proliferation and induced a dramatic change in cytoskeletal remodeling and FA rearrangement, detrimentally affecting CCM. Further analysis revealed that α4β1/α9β1 integrins suppress extracellular signal-regulated kinase (ERK1/2) activity to control migration through the regulation of downstream kinases including Mitogen and Stress Activated Kinase 1 (MSK1). This work demonstrates the roles of α4β1 and α9β1 in regulating migration in response to damage cues.

scholarly journals Supracellular organization confers directionality and mechanical potency to migrating pairs of cardiopharyngeal progenitor cells

2021 ◽  
Author(s):  
Yelena Y. Bernadskaya ◽  
Haicen Yue ◽  
Calina Copos ◽  
Lionel Christiaen ◽  
Alex Mogilner
Keyword(s):  
Cell Migration ◽  
Cell Communication ◽  
Biomechanical Properties ◽  
Collective Cell Migration ◽  
Cellular Potts Model ◽  
Cellular Mechanics ◽  
Cell Matrix ◽  
Collective Movements ◽  
Cell Matrix Adhesion

AbstractPhysiological and pathological morphogenetic events involve a wide array of collective movements, suggesting that these multicellular arrangements confer biochemical and biomechanical properties that contribute to tissue scale organization. The cardiopharyngeal progenitors of the tunicate Ciona provide the simplest possible model of collective cell migration. They form cohesive bilateral cell pairs, leader-trailer polarized along the migration path as they migrate between the ventral epidermis and trunk endoderm. Here, circumventing difficulties in quantifying cellular mechanics in live embryos, we use the Cellular Potts Model to computationally probe the distributions of forces consistent with the shapes and collective polarity of migrating cell pairs. Combining computational modeling, confocal microscopy, and molecular perturbations, we first determine that cardiopharyngeal progenitors display hallmarks of supracellular organization, with differential distributions of protrusive forces, cell-matrix adhesion, and myosin-based retraction forces along the leader-trailer axis. Combined 4D simulations and experimental observations suggest that cell-cell communication helps establish a hierarchy that contributes to aligning collective polarity with the direction of migration, as observed with three or more cells both in silico and in vivo. Our approach reveals emerging properties of the migrating collective. Specifically, cell pairs are more persistent, thus migrating over longer distances, and presumably with higher accuracy. Finally, simulations suggest that polarized cell pairs literally join forces to deform the trunk endoderm, as they migrate through the extracellular space. We thus propose that the polarized supracellular organization of cardiopharyngeal progenitors confers emergent physical properties that determine mechanical interactions with their environment during morphogenesis.

The Expression Signatures of Mammary Tumor Associated Macrophages.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3850-3850
Author(s):  
Laureen S. Ojalvo ◽  
Jeffrey W. Pollard
Keyword(s):  
Gene Expression ◽  
Flow Cytometry ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
Transcript Abundance ◽  
Carcinoma Cells ◽  
Tumor Cell Migration ◽  
Two Populations

Abstract It is well established that an increased density of tumor-associated macrophages (TAMs) correlates with poor prognosis in many types of solid tumors. This evidence is particularly strong for breast cancers. A causal relationship between TAMs and poor prognosis was suggested by experiments whereby a genetic depletion of macrophages in a mouse model of breast cancer caused by the mammary restricted expression of the Polyoma Middle T oncoprotein (PyMT) slowed tumor progression and inhibited metastasis. Subsequent studies in these primary mammary tumors showed that TAMs directly or indirectly promote tumor angiogenesis as well as tumor cell migration, invasion and intravasion. TAMs are also thought to affect the inflammatory context of the tumor microenvironment by suppressing adaptive immune responses that would normally reject the growing tumor. The varied tasks ascribed to TAMs suggested that the tumor microenvironment educates different population of macrophages to perform specific tasks. In this study, we isolated TAMs from the PyMT primary tumors in order to evaluate their gene expression signatures compared to a resident splenic population in order to define specific tumor associated functions. To perform these studies mice that express enhanced green fluorescent protein (eGFP) from the colony stimulating factor 1 receptor (CSF-1R) mononuclear phagocytic restricted promoter were crossed to the PyMT animals to generate offspring with eGFP+ TAMs. Animals were injected with dye-conjugated dextran two hours prior to sacrifice in order to identify phagocytic cells, a characteristic of macrophages. We have established that these eGFP+/dextran+ cells are F4/80+ and define the TAM population. EGFP+/dextran+ TAMs were isolated using flow cytometry from late-stage tumors and splenic macrophages were sorted from non-tumor bearing animals using an identical protocol. These two populations were analyzed on gene expression oligoarrays to better elucidate specific mediators of TAM pathogenicity. We have identified approximately 100 genes whose transcript abundance are up or down regulated in the TAM population including genes mediating angiogenesis, adhesion and inflammation. Furthermore, genes previously described to define the tumor associated suppressor macrophage (MIF-1, MIP1α and TGFβ, high; IL-18, low) were similarly regulated amongst the three biological repeats. To further define individual TAM populations, we used an in vivo invasion assay to isolate a subset of TAMs that promote carcinoma cell motility in vivo. This assay involves the collection of invasive tumor cells and co-migrating invasive TAMs into EGF-containing microneedles placed directly into the primary tumor of an MMTV-PyMT animal. Previously, this assay was used to describe a paracrine loop in which carcinoma cells secrete CSF-1 that binds CSF-1R on TAMs leading to TAM secretion of epidermal growth factor (EGF) that binds the EGF receptor on carcinoma cells and stimulate their motility. Disrupting this paracrine loop is known to block the invasion of both cell types. Invasive TAMs isolated via this assay and separated from invasive carcinoma cells using CD11b magnetic beads were compared by gene expression arrays to TAMs sorted by flow cytometry (F4/80+/dextran+). The transcript abundance of about 200 genes were differentially regulated between these two populations. Together, these two studies illustrate key genes expressed in TAMs that may regulate tumor progression and furthermore, define a specific sub-population of TAMs that directly promotes tumor cell migration and invasion.

scholarly journals Src42A required for collective border cell migration in vivo

2017 ◽  
Author(s):  
Yasmin Sallak ◽  
Alba Yurani Torres ◽  
Hongyan Yin ◽  
Denise Montell
Keyword(s):  
Cell Migration ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Border Cell ◽  
Border Cell Migration ◽  
And Migration ◽  
Drosophila Ovary ◽  
E Cadherin

AbstractThe tyrosine kinase Src is over-expressed in numerous human cancers and is associated with poor prognosis. While Src has been extensively studied, its contributions to collective cell migration in vivo remain incompletely understood. Here we show that Src42A, but not Src64, is required for the specification and migration of the border cells in the Drosophila ovary, a well-developed and genetically tractable in vivo cell migration model. We found active Src42A enriched at border cell/nurse cell interfaces, where E-cadherin is less abundant, and depleted from border cell/border cell and border cell/polar cell junctions where E-cadherin is more stable, whereas total Src42A protein co-localizes with E-cadherin. Over-expression of wild type Src42A mislocalized Src activity and prevented border cell migration. Constitutively active or kinase dead forms of Src42A also impeded border cells. These findings establish border cells as a model for investigating the mechanisms of action of Src in cooperative, collective, cell-on-cell migration in vivo.

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