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The gastrointestinal (GI) tract of metazoans is lined by a series of regionally distinct epithelia. To maintain structure and function of the GI tract, regionally diversified differentiation of somatic stem cell (SC) lineages is critical. The adult Drosophila midgut provides an accessible model to study SC regulation and specification in a regionally defined manner. SCs of the posterior midgut (PM) have been studied extensively, but the control of SCs in the middle midgut (MM) is less well understood. The MM contains a stomach-like copper cell region (CCR) that is regenerated by gastric stem cells (GSSCs) and contains acid-secreting copper cells (CCs). Bmp-like Decapentaplegic (Dpp) signaling determines the identity of GSSCs, and is required for CC regeneration, yet the precise control of Dpp signaling activity in this lineage remains to be fully established. Here, we show that Dad, a negative feedback regulator of Dpp signaling, is dynamically regulated in the GSSC lineage to allow CC differentiation. Dad is highly expressed in GSSCs and their first daughter cells, the gastroblasts (GBs), but has to be repressed in differentiating CCs to allow Dpp-mediated differentiation into CCs. We find that the Hox gene ultrabithorax (Ubx) is required for this regulation. Loss of Ubx prevents Dad repression in the CCR, resulting in defective CC regeneration. Our study highlights the need for dynamic control of Dpp signaling activity in the differentiation of the GSSC lineage and identifies Ubx as a critical regulator of this process.

Titel:	Ubx dynamically regulates Dpp signaling by repressing Dad expression during copper cell regeneration in the adult Drosophila midgut.
Autor/in / Beteiligte Person:	Li, H ; Qi, Y ; Jasper, H
Link:	Full Text Finder (Volltext)
Zeitschrift:	Developmental biology, Jg. 419 (2016-11-15), Heft 2, S. 373-381
Veröffentlichung:	San Diego, CA : Elsevier ; <i>Original Publication</i>: New York., 2016
Medientyp:	academicJournal
ISSN:	1095-564X (electronic)
DOI:	10.1016/j.ydbio.2016.08.027
Schlagwort:	Animals Cell Differentiation Cell Lineage Drosophila Proteins deficiency Drosophila Proteins genetics Drosophila melanogaster genetics Drosophila melanogaster growth & development Epithelial Cells metabolism Feedback, Physiological Female Gastric Acid metabolism Genes, Homeobox Genes, Reporter Homeodomain Proteins genetics Intestines cytology Nuclear Proteins physiology Signal Transduction Stem Cells metabolism Transcription Factors deficiency Transcription Factors genetics Copper metabolism Drosophila Proteins physiology Drosophila melanogaster metabolism Homeodomain Proteins physiology Intestines physiology Regeneration physiology Transcription Factors physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Dev Biol] 2016 Nov 15; Vol. 419 (2), pp. 373-381. <i>Date of Electronic Publication: </i>2016 Aug 25. MeSH Terms: Copper / metabolism ; Drosophila Proteins / physiology ; Drosophila melanogaster / metabolism ; Homeodomain Proteins / physiology ; Intestines / physiology ; Regeneration / physiology ; Transcription Factors / *physiology ; Animals ; Cell Differentiation ; Cell Lineage ; Drosophila Proteins / deficiency ; Drosophila Proteins / genetics ; Drosophila melanogaster / genetics ; Drosophila melanogaster / growth & development ; Epithelial Cells / metabolism ; Feedback, Physiological ; Female ; Gastric Acid / metabolism ; Genes, Homeobox ; Genes, Reporter ; Homeodomain Proteins / genetics ; Intestines / cytology ; Nuclear Proteins / physiology ; Signal Transduction ; Stem Cells / metabolism ; Transcription Factors / deficiency ; Transcription Factors / genetics References: Cell Stem Cell. 2010 Dec 3;7(6):656-70. (PMID: 21112561) ; Carcinogenesis. 2012 Oct;33(10):1985-92. (PMID: 22791809) ; Elife. 2013 Aug 27;2:e00886. 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(PMID: 9693372) Grant Information: R01 AG028127 United States AG NIA NIH HHS; R01 AG050104 United States AG NIA NIH HHS; R01 GM100196 United States GM NIGMS NIH HHS Contributed Indexing: Keywords: Drosophila; Intestinal stem cell; Regeneration; Ubx Substance Nomenclature: 0 (Dad protein, Drosophila) ; 0 (Drosophila Proteins) ; 0 (Homeodomain Proteins) ; 0 (Nuclear Proteins) ; 0 (Transcription Factors) ; 0 (Ubx protein, Drosophila) ; 0 (ct protein, Drosophila) ; 0 (dpp protein, Drosophila) ; 0 (lab protein, Drosophila) ; 789U1901C5 (Copper) Entry Date(s): Date Created: 20160830 Date Completed: 20170815 Latest Revision: 20200306 Update Code: 20240513 PubMed Central ID: PMC5681348

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Ubx dynamically regulates Dpp signaling by repressing Dad expression during copper cell regeneration in the adult Drosophila midgut.