title: The insulator protein BEAF-32 is required for Hippo pathway activity in the terminal differentiation of neuronal subtypes.
abstract: The Hippo pathway is crucial for not only normal growth and apoptosis but also cell fate specification during development. What controls Hippo pathway activity during cell fate specification is incompletely understood. In this article, we identify the insulator protein BEAF-32 as a regulator of Hippo pathway activity in Drosophila photoreceptor differentiation. Though morphologically uniform, the fly eye is composed of two subtypes of R8 photoreceptor neurons defined by expression of light-detecting Rhodopsin proteins. In one R8 subtype, active Hippo signaling induces Rhodopsin 6 (Rh6) and represses Rhodopsin 5 (Rh5), whereas in the other subtype, inactive Hippo signaling induces Rh5 and represses Rh6. The activity state of the Hippo pathway in R8 cells is determined by the expression of warts, a core pathway kinase, which interacts with the growth regulator melted in a double-negative feedback loop. We show that BEAF-32 is required for expression of warts and repression of melted Furthermore, BEAF-32 plays a second role downstream of Warts to induce Rh6 and prevent Rh5 fate. BEAF-32 is dispensable for Warts feedback, indicating that BEAF-32 differentially regulates warts and Rhodopsins. Loss of BEAF-32 does not noticeably impair the functions of the Hippo pathway in eye growth regulation. Our study identifies a context-specific regulator of Hippo pathway activity in post-mitotic neuronal fate, and reveals a developmentally specific role for a broadly expressed insulator protein.
authors.affiliation: Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jukam
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Kayla
authors.initials: K
authors.lastname: Viets
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: DeFord
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218-2685, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Yan
authors.affiliation: Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
authors.forename: Jinshuai
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218-2685, USA robertjohnston@jhu.edu.
authors.forename: Robert J
authors.identifier: 0000-0003-4419-0646
authors.initials: RJ
authors.lastname: Johnston
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D025461:Feedback, Physiological; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction; D000099317:Hippo Kinases
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D012243:Rhodopsin; C452919:BEAF-32 protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Cell fate; Color vision; Drosophila retina; Hippo pathway; Insulator; Photoreceptor; RNAi screen; Regulatory networks; Rhodopsin; Warts tumor suppressor