TY - JOUR TI - Drosophila hedgehog can act as a morphogen in the absence of regulated Ci processing AU - Little, Jamie C AU - Garcia-Garcia, Elisa AU - Sul, Amanda AU - Kalderon, Daniel A2 - Desplan, Claude A2 - Banerjee, Utpal A2 - Holmgren, Bob VL - 9 PY - 2020 DA - 2020/10/21 SP - e61083 C1 - eLife 2020;9:e61083 DO - 10.7554/eLife.61083 UR - https://doi.org/10.7554/eLife.61083 AB - Extracellular Hedgehog (Hh) proteins induce transcriptional changes in target cells by inhibiting the proteolytic processing of full-length Drosophila Ci or mammalian Gli proteins to nuclear transcriptional repressors and by activating the full-length Ci or Gli proteins. We used Ci variants expressed at physiological levels to investigate the contributions of these mechanisms to dose-dependent Hh signaling in Drosophila wing imaginal discs. Ci variants that cannot be processed supported a normal pattern of graded target gene activation and the development of adults with normal wing morphology, when supplemented by constitutive Ci repressor, showing that Hh can signal normally in the absence of regulated processing. The processing-resistant Ci variants were also significantly activated in the absence of Hh by elimination of Cos2, likely acting through binding the CORD domain of Ci, or PKA, revealing separate inhibitory roles of these two components in addition to their well-established roles in promoting Ci processing. KW - hedgehog KW - signaling KW - Ci KW - morphogen KW - Protein Kinase A KW - costal 2 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -