TY - JOUR
T1 - Binary regulation of Hippo pathway by Merlin/NF2, Kibra, Lgl, and melted specifies and maintains postmitotic neuronal fate
AU - Jukam, David
AU - Desplan, Claude
N1 - Funding Information:
We are grateful to S. Blair, S. Britt, S. Cohen, I. Davis, B. Dickson, R. Fehon, G. Halder, I. Hariharan, K. Irvine, J. Jiang, Z-C. Lai, A. Laughon, D. Pan, N. Tapon, J. Treisman, T. Xu, C. Zuker, and the Bloomington Stock Center for generously providing fly stocks and antibodies. We thank N. Baker, G. Halder, P. McKenney, P. Sood, and members of the C.D. laboratory for helpful discussions and comments on the manuscript. D.J. was supported by a New York University Dean's Dissertation Fellowship. C.D. was supported by NIH grant RO1 EY13012.
PY - 2011/11/15
Y1 - 2011/11/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.devcel.2011.10.004
DO - 10.1016/j.devcel.2011.10.004
M3 - Article
C2 - 22055343
AN - SCOPUS:80755175725
SN - 1534-5807
VL - 21
SP - 874
EP - 887
JO - Developmental Cell
JF - Developmental Cell
IS - 5
ER -