The contribution of specific cell subpopulations to submandibular salivary gland branching morphogenesis

Kwon, Hae Ryong; Larsen, Melinda

doi:10.1016/j.gde.2015.01.007

Cited by 18 publications

(13 citation statements)

References 69 publications

(87 reference statements)

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“…This complex, highly dynamic process remodels a simple epithelial bud into a highly arborized branched organ structure that maximizes epithelial surface area for secretion or absorption. Although many studies have highlighted requirements for numerous signaling molecules and transcription factors during branching morphogenesis (Costantini and Kopan, 2010;Harunaga et al, 2011;Hauser and Hoffman, 2015;Hennighausen and Robinson, 2005;Iber and Menshykau, 2013;Kwon and Larsen, 2015;Shih et al, 2013;Varner and Nelson, 2014), it is not fully understood at the cell and tissue level how such diverse regulatory pathways orchestrate the extensive physical remodeling that shapes branched epithelial tissues. Recent advances in microscopy have established that specific dynamic cell behaviors, such as changes in cell motility, cell-cell adhesion and cell-extracellular matrix interactions, are key functional mediators of this tissue reorganization (Daley and Yamada, 2013;Friedl and Gilmour, 2009;Harunaga et al, 2011;Huebner and Ewald, 2014;Kim and Nelson, 2012;Nelson and Larsen, 2015;Varner and Nelson, 2014).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Btbd7 is essential for region-specific epithelial cell dynamics and branching morphogenesis in vivo

et al. 2017

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Branching morphogenesis of developing organs requires coordinated but poorly understood changes in epithelial cell-cell adhesion and cell motility. We report that Btbd7 is a crucial regulator of branching morphogenesis in vivo. Btbd7 levels are elevated in peripheral cells of branching epithelial end buds, where it enhances cell motility and cellcell adhesion dynamics. Genetic ablation of Btbd7 in mice disrupts branching morphogenesis of salivary gland, lung and kidney. Btbd7 knockout results in more tightly packed outer bud cells, which display stronger E-cadherin localization, reduced cell motility and decreased dynamics of transient cell separations associated with cleft formation; inner bud cells remain unaffected. Mechanistic analyses using in vitro MDCK cells to mimic outer bud cell behavior establish that Btbd7 promotes loss of E-cadherin from cell-cell adhesions with enhanced migration and transient cell separation. Btbd7 can enhance E-cadherin ubiquitination, internalization, and degradation in MDCK and peripheral bud cells for regulating cell dynamics. These studies show how a specific regulatory molecule, Btbd7, can function at a local region of developing organs to regulate dynamics of cell adhesion and motility during epithelial branching morphogenesis.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Btbd7 is essential for region-specific epithelial cell dynamics and branching morphogenesis in vivo

et al. 2017

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“…Although we know a great deal about the impact of these signalling pathways in controlling morphogenesis, we are only beginning to understand their impact on progenitor/stem cell behavior. Here we will review those pathways known to regulate progenitor cells and point the reader to excellent reviews on pathways regulating tissue morphogenesis (Kwon and Larsen, 2015; Mattingly et al , 2015; Patel and Hoffman, 2014). …”

Section: Salivary Gland Developmentmentioning

confidence: 99%

“…Here we will review those pathways known to regulate progenitor cells and point the reader to excellent reviews on pathways regulating tissue morphogenesis (Kwon & Larsen, 2015;Mattingly et al, 2015;.…”

mentioning

confidence: 99%

Salivary gland stem cells: A review of development, regeneration and cancer

Emmerson

Knox

2018

Genesis

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Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by autoimmune diseases such as Sjögren's syndrome. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. However, these approaches have been hampered by a lack of knowledge on the identity of salivary stem cell populations and their regulators. In this review we discuss our current knowledge on salivary stem cells and their regulators during organ development, homeostasis and regeneration. As increasing evidence in other systems suggests that progenitor cells may be a source of cancer, we also review whether these same salivary stem cells may also be cancer initiating cells.

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“…In mice, SG morphogenesis begins during early embryonic development. The rudimentary salivary gland is first visible as a thickening of the adjoining oral epithelium which occurs at approximately embryonic day 11.5 (E11.5), commonly known as the Prebud stage 1 , 5 , 6 . During the subsequent Initial Bud stage (E12.5), the thickened epithelium invaginates into the underlying mesenchyme thus forming a primary bud which will serve as the precursor of the main duct of the salivary gland.…”

Section: Introductionmentioning

confidence: 99%

Genetic and scRNA-seq Analysis Reveals Distinct Cell Populations that Contribute to Salivary Gland Development and Maintenance

Song

Min

Oyelakin

et al. 2018

Sci Rep

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Stem and progenitor cells of the submandibular salivary gland (SMG) give rise to, maintain, and regenerate the multiple lineages of mature epithelial cells including those belonging to the ductal, acinar, basal and myoepithelial subtypes. Here we have exploited single cell RNA-sequencing and in vivo genetic lineage tracing technologies to generate a detailed map of the cell fate trajectories and branch points of the basal and myoepithelial cell populations of the mouse SMG during embryonic development and in adults. Our studies show that the transcription factor p63 and alpha-smooth muscle actin (SMA) serve as faithful markers of the basal and myoepithelial cell lineages, respectively and that both cell types are endowed with progenitor cell properties. However, p63+ basal and SMA+ myoepithelial cells exhibit distinct cell fates by virtue of maintaining different cellular lineages during morphogenesis and in adults. Collectively, our results reveal the dynamic and complex nature of the diverse SMG cell populations and highlight the distinct differentiation potential of the p63 and SMA expressing subtypes in the stem and progenitor cell hierarchy. Long term these findings have profound implications towards a better understanding of the molecular mechanisms that dictate lineage commitment and differentiation programs during development and adult gland maintenance.

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The contribution of specific cell subpopulations to submandibular salivary gland branching morphogenesis

Cited by 18 publications

References 69 publications

RETRACTED: Btbd7 is essential for region-specific epithelial cell dynamics and branching morphogenesis in vivo

RETRACTED: Btbd7 is essential for region-specific epithelial cell dynamics and branching morphogenesis in vivo

Salivary gland stem cells: A review of development, regeneration and cancer

Genetic and scRNA-seq Analysis Reveals Distinct Cell Populations that Contribute to Salivary Gland Development and Maintenance

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