title: Binary regulation of Hippo pathway by Merlin/NF2, Kibra, Lgl, and Melted specifies and maintains postmitotic neuronal fate.
abstract: Patterning the Drosophila retina for color vision relies on postmitotic specification of photoreceptor subtypes. R8 photoreceptors express one of two light-sensing Rhodopsins, Rh5 or Rh6. This fate decision involves a bistable feedback loop between Melted, a PH-domain protein, and Warts, a kinase in the Hippo growth pathway. Here, we show that a subset of the Hippo pathway-Merlin, Kibra, and Lethal(2)giant larvae (Lgl), but not Expanded or Fat-is required for Warts expression and activity in R8 to specify Rh6 fate. Melted represses warts transcription to disrupt Hippo pathway activity and specify Rh5 fate. Therefore, R8 Hippo signaling exhibits ON-or-OFF regulation, promoting mutually exclusive fates. Furthermore, Merlin and Lgl are continuously required to maintain R8 neuronal subtypes. These results reveal roles for Merlin, Kibra, and Lgl in neuronal specification and maintenance and show that the Hippo pathway is reimplemented for sensory neuron fate by combining canonical and noncanonical regulatory steps.
authors: Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
authors: David
authors: D
authors: Jukam
authors: Claude
authors: C
authors: Desplan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008938:Mitosis; D025581:Neurofibromin 2 / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D025581:Neurofibromin 2; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C548168:kibra protein, Drosophila; C081435:l(2)gl protein, Drosophila; C099885:merlin, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases