Developing human minor salivary glands: morphological parallel relation between the expression of TGF-beta isoforms and cytoskeletal markers of glandular maturation

Lourenço, Sílvia Vanessa; Uyekita, Sabrina Hitomi; Lima, Danielle Malta; Soares, Fernando Augusto

doi:10.1007/s00428-007-0552-y

Cited by 22 publications

(23 citation statements)

References 30 publications

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“…The SG differentiates through a process known as branching morphogenesis that requires TGF-β (Jaskoll and Melnick, 1999; Lourenco et al, 2008). Specifically, TGF-β induces the expression of E-cadherin and fibronectin in the clefts that deepen into primordial glandular buds creating branches.…”

Section: Resultsmentioning

confidence: 99%

“…All TGF-β isoforms are expressed in the SGs during development and have an important role in glandular organogenesis, influencing branching morphogenesis and extracellular matrix deposition (Jaskoll and Melnick, 1999; Lourenco et al, 2008). We postulate that the increasing production of TGF-β during development and its persistence in large amounts drives the differentiation and maintenance of ILCs.…”

Section: Discussionmentioning

confidence: 99%

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Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands

et al. 2016

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Summary The signals guiding differentiation of innate lymphoid cells (ILCs) within tissues are not well understood. Salivary gland (SG) ILCs as well as liver and intestinal intraepithelial ILC1 have markers that denote tissue residency and transforming growth factor–β (TGF-β) imprinting. We deleted Tgfbr2 in cells expressing the ILC and NK marker NKp46 and found that SG ILCs were reduced in number. They lost distinct tissue markers, such as CD49a, and the effector molecules TRAIL and CD73. Expression of the transcription factor Eomes, which promotes NK cell differentiation, was elevated. Conversely, Eomes deletion in NKp46+ cells enhanced TGF-β-imprinting of SG ILCs. Thus, TGF-β induces SG ILC differentiation by suppressing Eomes. TGF-β acted through a JNK-dependent, Smad4-independent pathway. Transcriptome analysis demonstrated that SG ILCs had characteristic of both NK cells and ILC1. Finally, TGF-β imprinting of SG ILCs was synchronized with SG development, highlighting the impact of tissue microenvironment on ILC development

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands

et al. 2016

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“…The developmental pattern of human SGs has already been described as following a similar process compared to the mouse (Lourenço, Uyekita, Lima, & Soares, 2008;Teshima et al, 2011), although little is known about the role of apoptosis during human glandular morphogenesis. The expression of apoptosis-related proteins analysed in this study support a role for programmed cell death in gland development, particularly during lumen formation agreeing with recent research from the mouse (Teshima et al, 2016), however in the human samples apoptosis did not appear to involve the cleavage of the well-known downstream apoptotic regulator caspase-3.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-associated protein expression in human salivary gland morphogenesis

Teshima

Ianez

Coutinho‐Camillo

et al. 2016

Archives of Oral Biology

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Objective: Salivary gland (SG) development is based on branching morphogenesis, in which programmed cell death has been proposed to play a role in cell signalling and organ shaping.In the mouse salivary gland apoptosis has been suggested to play a key role in lumen formation, removing the central cells of the epithelial stalks. Here we analyse the expression of several anti-and pro-regulators of apoptosis during human SG development in a range of developmental stages.Design: Foetal SGs obtained from the University of São Paulo were analysed by immunohistochemistry to assess the expression of apoptosis-associated proteins: caspases (caspase-6, -7, -9 and cleaved caspase-3), Bcl-2 family members (Bax, Bak, Bad, Bid, Bcl-2, Bcl-x and Bcl-xL), Survivin (BIRC5), Cytochrome C and Apaf-1.Results: Nuclear expression of Bax and Bak was identified in presumptive luminal areas at initial stages, while Bcl-xL showed the most relevant anti-apoptotic activity. Caspase-6, -7 and -9 were expressed during all stages, while interestingly cleaved caspase-3 showed no prominent expression, indicating that caspase-7 is the main effector. Apoptosome complex components Apaf-1 and Cytochrome C, as well as survivin were all positive in developing glands. Conclusions:The particular expression pattern of several apoptotic regulators in human SG development suggests the existence of a fundamental role for apoptosis during duct formation. The absence of Bad and Bid expressions indicates that the instrinsic pathway is more active then the extrinsic during human gland formation. The subcellular localisation of intrinsic-apoptosis proteins correlated with apoptotic activity, but also suggested additional non-apoptotic functions. Highlights: Caspase-7 is the main executioner caspase involved in human SG duct development  Consistent cytoplasmic expression suggest additional non-apoptotic functions  Intrinsic-type apoptotic pathway drives human SG development

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“…The epithelial ingrowths constitute the parenchyma of a salivary gland. The ectomesenchyme differentiates into the connective tissue component of the gland, which supports the glandular parenchyma (Dale, 1994;Klein, 1994;Lourenço et al 2007Lourenço et al , 2008.…”

Section: Introductionmentioning

confidence: 99%

Development of human minor salivary glands: expression of mucins according to stage of morphogenesis

et al. 2011

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The formation of salivary glands entails the proliferation of epithelial cells from the stomatodeum into the underlying ectomesenchyme, culminating in a complex network of ducts and acinar bulbs. The extent to which mucins regulate this process is unknown, but they appear to mediate luminal space formation and maturation. Our aim was to examine mucin expression patterns during the morphogenesis of human salivary glands. Mucin expression -MUC1, 2, 3, 4, 5AC, 5B, 6, and 16 -was analyzed in specimens of developing human salivary glands, obtained from fetuses at 4-24 weeks' gestation, and fully developed salivary glands by immunohistochemistry. Expression patterns were analyzed qualitatively according to the development stage of the salivary glands. Mucins 1, 3, 4, 5B, and 16 were expressed during salivary gland development -being stronger in all ductal segments by the final phases of branching morphogenesis and in mature glands. Acinar cells were negative for most mucins, including MUC1 in mature salivary glands. Mucins 2, 5AC, and 6 were not expressed. Mucins MUC1, 3, 4, 5B, and 16 are expressed in developing human salivary glands and in mature glands, suggesting important roles in the maturation and maintenance of the ductal network.

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Developing human minor salivary glands: morphological parallel relation between the expression of TGF-beta isoforms and cytoskeletal markers of glandular maturation

Cited by 22 publications

References 30 publications

Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands

Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands

Apoptosis-associated protein expression in human salivary gland morphogenesis

Development of human minor salivary glands: expression of mucins according to stage of morphogenesis

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