title: Ubx dynamically regulates Dpp signaling by repressing Dad expression during copper cell regeneration in the adult Drosophila midgut.
abstract: 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.
authors: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA.
authors: Hongjie
authors: H
authors: Li
authors: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors: Yanyan
authors: Y
authors: Qi
authors: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA. Electronic address: hjasper@buckinstitute.org.
authors: Heinrich
authors: H
authors: Jasper
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D003300:Copper / Q000378:metabolism*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D025461:Feedback, Physiological; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005801:Genes, Homeobox; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007422:Intestines / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C108633:Dad protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; C066381:ct protein, Drosophila; C064196:dpp protein, Drosophila; C059843:lab protein, Drosophila; D003300:Copper
keywords: Drosophila; Intestinal stem cell; Regeneration; Ubx