Journal
DEVELOPMENT
Volume 133, Issue 18, Pages 3517-3527Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.02525
Keywords
Drosophila; fork head (Fkh); prolyl-4-hydroxylase; sage; salivary gland; tube morphogenesis
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Funding
- NIDCR NIH HHS [R01 DE13899] Funding Source: Medline
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(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: PH4 alpha SG1 and PH4 alpha SG2. 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 PH4 alpha SG2, as well as sage itself, and to indirectly regulate expression of PH4 alpha SG1. PH4 alpha SG1 and PH4 alpha SG2 encode alpha-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 PH4 alpha SG1 and PH4 alpha SG2; 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 PH4 alpha SG1 and PH4 alpha SG2 link Fkh, which initiates tube formation, to the maintenance of an open and uniformly sized secretory tube.
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