Conditional knockout of fibronectin abrogates mouse mammary gland lobuloalveolar differentiation

Liu, Keyi; Cheng, Lei; Flesken‐Nikitin, Andrea; Huang, Lynn Y.L.; Nikitin, Alexander Yu.; Pauli, Bendicht U.

doi:10.1016/j.ydbio.2010.07.001

Cited by 33 publications

(26 citation statements)

References 58 publications

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“…However, recent in vivo studies suggest that in addition to paracrine functions (Yoshino et al, 2014), Fn1 could also signal in a cell-autonomous manner (Cseh et al, 2010;Liu et al, 2010;Serres et al, 2014;Stenzel et al, 2011). By using genetic and cell biological approaches, the studies reported in this paper are the first to demonstrate the requisite, cell-autonomous role of Fn1 in the regulation of cardiovascular development.…”

Section: Role Of Fn1 and Integrin α5 In Nc Development And Cardiovascmentioning

confidence: 81%

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Wang

Astrof

2015

Development

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The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into vascular smooth muscle cells (VSMCs) by regulating Notch signaling. We show that NC Fn1 signals in an NC cell-autonomous manner through integrin α5β1 expressed by the NC, leading to activation of Notch and differentiation of VSMCs. Our data demonstrate an essential role of the localized synthesis of Fn1 in cardiovascular development and spatial regulation of Notch signaling.

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Section: Role Of Fn1 and Integrin α5 In Nc Development And Cardiovascmentioning

confidence: 81%

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Wang

Astrof

2015

Development

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“…In fact, both fibronectin and Slug have been consistently implicated in driving luminal progenitor cell proliferation and lobuloaveolar structure formation as part of the development of the mammary gland. 35,39,49 Based on these observations, we speculate that CD151 removal induces Slug expression in the luminal progenitor cells, and subsequently increases the expression of Slug target genes, including fibronectin and tenascin C. As a result of such genetic re-programing, progenitor cells escape from ECMmediated constraint or quiescent state to acquire greater proliferating and differentiating activities, thereby enhancing tertiary branching of the mammary gland. In this manner, CD151 negatively regulates the formation of lobuloalveolar structures during mammary gland development, in contrast to the effect of disrupting fibronectin, FAK or b1 integrin.…”

Section: Cd151 As a Potential Functional Regulator Of Mammary Epithelmentioning

confidence: 83%

“…1-3), we evaluated the impact of CD151 removal on integrin-mediated cell-ECM interactions, as they are consistently implicated in driving the formation of lobuloalveolar structures during mammary gland development. 35,36 As shown in Figure 4A, expression of fibronectin, and to a lesser extent, tenascin C, exhibited a marked increase in mammary tissues upon CD151 removal. Also, the expression of fibronectin in TEBs was markedly elevated (Fig.…”

Section: Cd151 Removal Alters Ecm Composition and Fak Activation In Mmentioning

confidence: 91%

CD151 represses mammary gland development by maintaining the niches of progenitor cells

et al. 2014

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Tetraspanin CD151 interacts with laminin-binding integrins (i.e., a3b1, a6b1 and a6b4) and other cell surface molecules to control diverse cellular and physiological processes, ranging from cell adhesion, migration and survival to tissue architecture and homeostasis. Here, we report a novel role of CD151 in maintaining the branching morphogenesis and activity of progenitor cells during the pubertal development of mammary glands. In contrast to the disruption of laminin-binding integrins, CD151 removal in mice enhanced the tertiary branching in mammary glands by 2.4-fold and the number of terminal end buds (TEBs) by 30%, while having minimal influence on either primary or secondary ductal branching. Consistent with these morphological changes are the skewed distribution of basal/ myoepithelial cells and a 3.2-fold increase in proliferating Ki67-positive cells. These novel observations suggest that CD151 impacts the branching morphogenesis of mammary glands by upregulating the activities of bipotent progenitor cells. Indeed, our subsequent analyses indicate that upon CD151 removal the proportion of CD24 Hi CD49f Low progenitor cells in the mammary gland increased by 34%, and their proliferating and differentiating activities were significantly upregulated. Importantly, fibronectin, a pro-branching extracellular matrix (ECM) protein deposited underlying mammary epithelial or progenitor cells, increased by >7.2-fold. Moreover, there was a concomitant increase in the expression and nuclear distribution of Slug, a transcription factor implicated in the maintenance of mammary progenitor cell activities. Taken together, our studies demonstrate that integrin-associated CD151 represses mammary branching morphogenesis by controlling progenitor cell activities, ECM integrity and transcription program.

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“…A conditional knockout of fibronectin in the mammary gland resulted in decreased β1 integrin and FAK phosphorylation and abrogated alveologenesis and ductal outgrowth in pregnant mice (Liu et al 2010). The cells of these glands also showed a decrease in phosphorylated Erk1/2, cyclin D1, phosphorylated Stat5, and diminished proliferative capacity (Nagy et al 2007).…”

Section: Adhesion Signaling In Mammary Epithelial Cell Differentiatiomentioning

confidence: 99%

The contribution of adhesion signaling to lactogenesis

Morrison

Cutler

2010

Journal of Cell Communication and Signaling

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The mammary gland undergoes hormonally controlled cycles of pubertal maturation, pregnancy, lactation, and involution, and these processes rely on complex signaling mechanisms, many of which are controlled by cell-cell and cell-matrix adhesion. The adhesion of epithelial cells to the extracellular matrix initiates signaling mechanisms that have an impact on cell proliferation, survival, and differentiation throughout lactation. The control of integrin expression on the mammary epithelial cells, the composition of the extracellular matrix and the presence of secreted matricellular proteins all contribute to essential adhesion signaling during lactogenesis. In vitro and in vivo studies, including the results from genetically engineered mice, have shed light on the regulation of these processes at the cell and tissue level and have led to increased understanding of the essential signaling components that are regulated in temporal and cell specific manner during lactogenesis. Recent studies suggest that a secreted matricellular protein, CTGF/CCN2, may play a role in lactogenic differentiation through binding to β1 integrin complexes, enhancing the production of extracellular matrix components and contributions to cell adhesion signaling.

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Conditional knockout of fibronectin abrogates mouse mammary gland lobuloalveolar differentiation

Cited by 33 publications

References 58 publications

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

CD151 represses mammary gland development by maintaining the niches of progenitor cells

The contribution of adhesion signaling to lactogenesis

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