ArticleBMC developmental biology2009
Salivary gland branching morphogenesis: a quantitative systems analysis of the Eda/Edar/NFkappaB paradigm.
Article in BMC developmental biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Transcription factor FoxO1 regulates myoepithelial cell diversity and growth.Scientific reports · 2024Article
- Submandibular gland epithelial development and the importance of junctions.Tissue barriers · 2023Review
- Sci-Seq of Human Fetal Salivary Tissue Introduces Human Transcriptional Paradigms and a Novel Cell Population.Frontiers in dental medicine · 2022Article
- Role of the hedgehog signaling pathway in rheumatic diseases: An overview.Frontiers in immunology · 2022Review
- Defective NaCl Reabsorption in Salivary Glands of Eda-Null X-LHED Mice.Journal of dental research · 2018Article
- A novel role for cilia-dependent sonic hedgehog signaling during submandibular gland development.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Article
- Ectodysplasin A protein promotes corneal epithelial cell proliferation.The Journal of biological chemistry · 2017Article
- Downstream activation of NF-κB in the EDA-A1/EDAR signalling in Sjögren's syndrome and its regulation by the ubiquitin-editing enzyme A20.Clinical and experimental immunology · 2016Article
- CMV-induced embryonic mouse organ of corti dysplasia: Network architecture of dysfunctional lateral inhibition.Birth defects research. Part A, Clinical and molecular teratology · 2015Article
- Mechanistic modeling confronts the complexity of molecular cell biology.Molecular biology of the cell · 2014Article
- Molecular cues for development and regeneration of salivary glands.Histology and histopathology · 2014Review
- An in vitro mouse model of congenital cytomegalovirus-induced pathogenesis of the inner ear cochlea.Birth defects research. Part A, Clinical and molecular teratology · 2013Article
- Article
- Viral gene transfer to developing mouse salivary glands.Journal of dental research · 2012Article
- Capability of tissue stem cells to organize into salivary rudiments.Stem cells international · 2012Article
- A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene.BMC genetics · 2011Article
- Dynamics of salivary gland morphogenesis.Journal of dental research · 2011Review
- Small molecule inhibitors of the host cell COX/AREG/EGFR/ERK pathway attenuate cytomegalovirus-induced pathogenesis.Experimental and molecular pathology · 2011Article
- Systems analysis of salivary gland development and disease.Wiley interdisciplinary reviews. Systems biology and medicineReview
- Salivary gland development and disease.Wiley interdisciplinary reviews. Developmental biologyReview
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEctodysplasin-A appears to be a critical component of branching morphogenesis. Mutations in mouse Eda or human EDA are associated with absent or hypoplastic sweat glands, sebaceous glands, lacrimal glands, salivary glands (SMGs), mammary glands and/or nipples, and mucous glands of the bronchial, esophageal and colonic mucosa. In this study, we utilized EdaTa (Tabby) mutant mice to investigate how a marked reduction in functional Eda propagates with time through a defined genetic subcircuit and to test the proposition that canonical NFkappaB signaling is sufficient to account for the differential expression of developmentally regulated genes in the context of Eda polymorphism.
resultsThe quantitative systems analyses do not support the stated hypothesis. For most NFkappaB-regulated genes, the observed time course of gene expression is nearly unchanged in Tabby (EdaTa) as compared to wildtype mice, as is NFkappaB itself. Importantly, a subset of genes is dramatically differentially expressed in Tabby (Edar, Fgf8, Shh, Egf, Tgfa, Egfr), strongly suggesting the existence of an alternative Eda-mediated transcriptional pathway pivotal for SMG ontogeny. Experimental and in silico investigations have identified C/EBPalpha as a promising candidate.
conclusionIn Tabby SMGs, upregulation of the Egf/Tgfalpha/Egfr pathway appears to mitigate the potentially severe abnormal phenotype predicted by the downregulation of Fgf8 and Shh. Others have suggested that the buffering of the phenotypic outcome that is coincident with variant Eda signaling could be a common mechanism that permits viable and diverse phenotypes, normal and abnormal. Our results support this proposition. Further, if branching epithelia use variations of a canonical developmental program, our results are likely applicable to understanding the phenotypes of other branching organs affected by Eda (EDA) mutation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.