Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis

Lee, KangAe; Gjorevski, Nikolce; Boghaert, Eline; Radisky, Derek C.; Nelson, Celeste M.

doi:10.1038/emboj.2011.159

Cited by 64 publications

(56 citation statements)

References 56 publications

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“…Furthermore, most models propose that EMT occurs at the epithelial-stromal or tumor-stromal border (Lee et al, 2011). We see the opposite; the highest level of E-cadherin staining and the ultrastructurally highest degree of epithelial organization is at the luminal and basal surfaces of the tissue.…”

Section: Mammary Epithelial Cells Display Extensive Protrusive Activimentioning

confidence: 88%

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

Ewald

Huebner

Pálsdóttir

et al. 2012

Journal of Cell Science

136

137

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SummaryNormal mammary morphogenesis involves transitions between simple and multilayered epithelial organizations. We used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayered epithelium. We found that multilayered elongating ducts had polarized apical and basal tissue surfaces both in threedimensional culture and in vivo. However, individual cells were only polarized on surfaces in contact with the lumen or extracellular matrix. The basolateral marker scribble and the apical marker atypical protein kinase C zeta localized to all interior cell membranes, whereas PAR3 displayed a cytoplasmic localization, suggesting that the apico-basal polarity was incomplete. Despite membrane localization of E-cadherin and b-catenin, we did not observe a defined zonula adherens connecting interior cells. Instead, interior cells were connected through desmosomes and exhibited complex interdigitating membrane protrusions. Single-cell labeling revealed that individual cells were both protrusive and migratory within the epithelial multilayer. Inhibition of Rho kinase (ROCK) further reduced intercellular adhesion on apical and lateral surfaces but did not disrupt basal tissue organization. Following morphogenesis, segregated membrane domains were re-established and junctional complexes re-formed. We observed similar epithelial organization during mammary morphogenesis in organotypic culture and in vivo. We conclude that mammary epithelial morphogenesis involves a reversible, spatially limited, reduction in polarity and intercellular junctions and active individualistic cell migration. Our data suggest that reductions in polarity and adhesion during breast cancer progression might reflect partial recapitulation of a normal developmental program.

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Section: Mammary Epithelial Cells Display Extensive Protrusive Activimentioning

confidence: 88%

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

Ewald

Huebner

Pálsdóttir

et al. 2012

Journal of Cell Science

136

137

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“…Finally, expression of a late HSV-1 gene (VP16), which activates expression of IE genes (70), was proposed to stimulate reactivation from latency (83). Slug family members, including Snail1 and Snail2, also reduce expression of at least two proapoptotic proteins (Bid and p53) and consequently inhibit apoptosis (44,45). Perhaps increased levels of Slug promote successful reactivation from latency by enhancing the survival of latently infected neurons after DEX treatment.…”

Section: Discussionmentioning

confidence: 99%

Cellular Transcription Factors Induced in Trigeminal Ganglia during Dexamethasone-Induced Reactivation from Latency Stimulate Bovine Herpesvirus 1 Productive Infection and Certain Viral Promoters

Workman

Eudy

Smith

et al. 2012

J Virol

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Bovine herpesvirus 1 (BHV-1), an alphaherpesvirinae subfamily member, establishes latency in sensory neurons. Elevated corticosteroid levels, due to stress, reproducibly triggers reactivation from latency in the field. A single intravenous injection of the synthetic corticosteroid dexamethasone (DEX) to latently infected calves consistently induces reactivation from latency. Lytic cycle viral gene expression is detected in sensory neurons within 6 h after DEX treatment of latently infected calves. These observations suggested that DEX stimulated expression of cellular genes leads to lytic cycle viral gene expression and productive infection. In this study, a commercially available assay-Bovine Gene Chip-was used to compare cellular gene expression in the trigeminal ganglia (TG) of calves latently infected with BHV-1 versus DEX-treated animals. Relative to TG prepared from latently infected calves, 11 cellular genes were induced more than 10-fold 3 h after DEX treatment. Pentraxin three, a regulator of innate immunity and neurodegeneration, was stimulated 35-to 63-fold after 3 or 6 h of DEX treatment. Two transcription factors, promyelocytic leukemia zinc finger (PLZF) and Slug were induced more than 15-fold 3 h after DEX treatment. PLZF or Slug stimulated productive infection 20-or 5-fold, respectively, and Slug stimulated the late glycoprotein C promoter more than 10-fold. Additional DEX-induced transcription factors also stimulated productive infection and certain viral promoters. These studies suggest that DEX-inducible cellular transcription factors and/or signaling pathways stimulate lytic cycle viral gene expression, which subsequently leads to successful reactivation from latency in a small subset of latently infected neurons. Bovine herpesvirus 1 (BHV-1) is an alphaherpesvirinae subfamily member that causes significant economical losses to the cattle industry (86). The ability of BHV-1 to suppress the immune system can result in life-threatening pneumonia due to secondary bacterial infections. This multifactorial disorder is referred to as bovine respiratory disease complex (reviewed in references 35 and 39). Like different alphaherpesvirinae subfamily members, the primary site for BHV-1 latency is sensory neurons within trigeminal ganglia (TG). Viral gene expression (73) and infectious virus (29) are detected in TG from 1 to 6 days after acute infection. Lytic cycle viral gene expression is subsequently extinguished in sensory neurons, and latency is established. The BHV-1 genome is stably maintained in sensory neurons, but infectious virus is not detected by standard virus isolation procedures (reviewed in references 33 and 34). The only viral gene abundantly expressed in latently infected sensory neurons is the latency-related (LR) gene (reviewed in reference 38). Stress, due to confinement, transporting cattle, restricting food and water, weaning, or increased corticosteroid levels increases the incidence of reactivation from latency (35, 39). The latency reactivation cycle of BHV-1 is crucial for vi...

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“…The mechanical properties (elastic modulus and crosslinking) of the surrounding ECM regulate the profile of mechanical stress and branch initiation (Gjorevski and Nelson, 2010), and are also affected by matrix remodeling induced by contraction of the epithelium (Gjorevski and Nelson, 2012). Such ECM-mediated mechanical stresses regulate the expression of mesenchymal genes, including those encoding transcription factors such as Snail and Slug, within branch sites (Lee et al, 2011). As these genes are also expressed at branch sites within the mammary epithelium in vivo, it is possible that they are induced by the collagen fibrils already present in the mesenchyme.…”

Section: Matrix-driven Branchingmentioning

confidence: 99%

Cellular and physical mechanisms of branching morphogenesis

2014

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Branching morphogenesis is the developmental program that builds the ramified epithelial trees of various organs, including the airways of the lung, the collecting ducts of the kidney, and the ducts of the mammary and salivary glands. Even though the final geometries of epithelial trees are distinct, the molecular signaling pathways that control branching morphogenesis appear to be conserved across organs and species. However, despite this molecular homology, recent advances in cell lineage analysis and real-time imaging have uncovered surprising differences in the mechanisms that build these diverse tissues. Here, we review these studies and discuss the cellular and physical mechanisms that can contribute to branching morphogenesis.

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Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis

Cited by 64 publications

References 56 publications

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

Cellular Transcription Factors Induced in Trigeminal Ganglia during Dexamethasone-Induced Reactivation from Latency Stimulate Bovine Herpesvirus 1 Productive Infection and Certain Viral Promoters

Cellular and physical mechanisms of branching morphogenesis

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