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Fork head and Sage maintain a uniform and patent salivary gland lumen through regulation of two downstream target genes,PH4αSG1andPH4αSG2

doi: 10.1242/dev.02525
pmid: 16914497
Fork head and Sage maintain a uniform and patent salivary gland lumen through regulation of two downstream target genes,PH4αSG1andPH4αSG2
(Fkh) is required to block salivary gland apoptosis, internalize salivary gland precursors, prevent expression of duct genes in secretory cells and maintain expression of CrebA, which is required for elevated secretory function. Here, we characterize two new Fkh-dependent genes: PH4αSG1 and PH4αSG2. We show through in vitro DNA-binding studies and in vivo expression assays that Fkh cooperates with the salivary gland-specific bHLH protein Sage to directly regulate expression of PH4αSG2, as well as sage itself, and to indirectly regulate expression of PH4αSG1. PH4αSG1 and PH4αSG2 encode α-subunits of resident ER enzymes that hydroxylate prolines in collagen and other secreted proteins. We demonstrate that salivary gland secretions are altered in embryos missing function of PH4αSG1 and PH4αSG2; secretory content is reduced and shows increased electron density by TEM. Interestingly, the altered secretory content results in regions of tube dilation and constriction, with intermittent tube closure. The regulation studies and phenotypic characterization of PH4αSG1 and PH4αSG2 link Fkh, which initiates tube formation, to the maintenance of an open and uniformly sized secretory tube.
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
Microscopy, Confocal, Procollagen-Proline Dioxygenase, Gene Expression Regulation, Developmental, Nuclear Proteins, Electrophoretic Mobility Shift Assay, Forkhead Transcription Factors, Cyclic AMP Response Element-Binding Protein A, Immunohistochemistry, Salivary Glands, Drosophila melanogaster, Microscopy, Electron, Transmission, Basic Helix-Loop-Helix Transcription Factors, Morphogenesis, Animals, Drosophila Proteins, Salivary Proteins and Peptides, In Situ Hybridization, Transcription Factors
Microscopy, Confocal, Procollagen-Proline Dioxygenase, Gene Expression Regulation, Developmental, Nuclear Proteins, Electrophoretic Mobility Shift Assay, Forkhead Transcription Factors, Cyclic AMP Response Element-Binding Protein A, Immunohistochemistry, Salivary Glands, Drosophila melanogaster, Microscopy, Electron, Transmission, Basic Helix-Loop-Helix Transcription Factors, Morphogenesis, Animals, Drosophila Proteins, Salivary Proteins and Peptides, In Situ Hybridization, Transcription Factors
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