@article{2e981357a4f44de682fa18bdb4edf90d,
title = "Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling",
abstract = "De novo truncations in Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL) lead to severe childhood-onset neurodegenerative disorders. To determine how loss of IRF2BPL causes neural dysfunction, we examined its function in Drosophila and zebrafish. Overexpression of either IRF2BPL or Pits, the Drosophila ortholog, represses Wnt transcription in flies. In contrast, neuronal depletion of Pits leads to increased wingless (wg) levels in the brain and is associated with axonal loss, whereas inhibition of Wg signaling is neuroprotective. Moreover, increased neuronal expression of wg in flies is sufficient to cause age-dependent axonal loss, similar to reduction of Pits. Loss of irf2bpl in zebrafish also causes neurological defects with an associated increase in wnt1 transcription and downstream signaling. WNT1 is also increased in patient-derived astrocytes, and pharmacological inhibition of Wnt suppresses the neurological phenotypes. Last, IRF2BPL and the Wnt antagonist, CKIα, physically and genetically interact, showing that IRF2BPL and CkIα antagonize Wnt transcription and signaling.",
author = "{Undiagnosed Diseases Network} and Marcogliese, {Paul C.} and Debdeep Dutta and Ray, {Shrestha Sinha} and Dang, {Nghi D.P.} and Zhongyuan Zuo and Yuchun Wang and Di Lu and Fatima Fazal and Ravenscroft, {Thomas A.} and Hyunglok Chung and Oguz Kanca and Wan, {Ji Jun} and Douine, {Emilie D.} and Pena, {Loren D.M.} and Shinya Yamamoto and Nelson, {Stanley F.} and Matthew Might and Meyer, {Kathrin C.} and Yeo, {Nan Cher} and Bellen, {Hugo J.} and Acosta, {Maria T.} and Margaret Adam and Adams, {David R.} and Agrawal, {Pankaj B.} and Alejandro, {Mercedes E.} and Justin Alvey and Laura Amendola and Ashley Andrews and Ashley, {Euan A.} and Azamian, {Mahshid S.} and Bacino, {Carlos A.} and Guney Bademci and Eva Baker and Ashok Balasubramanyam and Dustin Baldridge and Jim Bale and Michael Bamshad and Deborah Barbouth and Pinar Bayrak-Toydemir and Anita Beck and Beggs, {Alan H.} and Edward Behrens and Gill Bejerano and Jimmy Bennet and Beverly Berg-Rood and Bernstein, {Jonathan A.} and Berry, {Gerard T.} and Anna Bican and Stephanie Bivona and Elizabeth Blue and John Bohnsack and Carsten Bonnenmann and Devon Bonner and Lorenzo Botto and Brenna Boyd and Briere, {Lauren C.} and Elly Brokamp and Gabrielle Brown and Burke, {Elizabeth A.} and Burrage, {Lindsay C.} and Butte, {Manish J.} and Peter Byers and Byrd, {William E.} and John Carey and Olveen Carrasquillo and Chang, {Ta Chen Peter} and Sirisak Chanprasert and Chao, {Hsiao Tuan} and Clark, {Gary D.} and Coakley, {Terra R.} and Cobban, {Laurel A.} and Cogan, {Joy D.} and Matthew Coggins and Cole, {F. Sessions} and Colley, {Heather A.} and Cooper, {Cynthia M.} and Heidi Cope and Craigen, {William J.} and Crouse, {Andrew B.} and Michael Cunningham and Precilla D'Souza and Hongzheng Dai and Surendra Dasari and Joie Davis and Dayal, {Jyoti G.} and Matthew Deardorff and Dell'Angelica, {Esteban C.} and Dhar, {Shweta U.} and Katrina Dipple and Daniel Doherty and Naghmeh Dorrani and Doss, {Argenia L.} and Draper, {David D.} and Laura Duncan and Dawn Earl and Eckstein, {David J.} and Emrick, {Lisa T.} and Eng, {Christine M.} and Cecilia Esteves and Marni Falk and Liliana Fernandez and Carlos Ferreira and Fieg, {Elizabeth L.} and Findley, {Laurie C.} and Fisher, {Paul G.} and Fogel, {Brent L.} and Irman Forghani and Gahl, {William A.} and Ian Glass and Bernadette Gochuico and Godfrey, {Rena A.} and Katie Golden-Grant and Goldman, {Alica M.} and Goldrich, {Madison P.} and Goldstein, {David B.} and Alana Grajewski and Groden, {Catherine A.} and Irma Gutierrez and Sihoun Hahn and Rizwan Hamid and Hanchard, {Neil A.} and Athena Hantzaridis and Kelly Hassey and Nichole Hayes and Frances High and Anne Hing and Hisama, {Fuki M.} and Holm, {Ingrid A.} and Jason Hom and Martha Horike-Pyne and Alden Huang and Yong Huang and Laryssa Huryn and Rosario Isasi and Fariha Jamal and Jarvik, {Gail P.} and Jeffrey Jarvik and Suman Jayadev and Lefkothea Karaviti and Jennifer Kennedy and Dana Kiley and Kobren, {Shilpa N.} and Kohane, {Isaac S.} and Kohler, {Jennefer N.} and Deborah Krakow and Krasnewich, {Donna M.} and Elijah Kravets and Susan Korrick and Mary Koziura and Krier, {Joel B.} and Lalani, {Seema R.} and Byron Lam and Christina Lam and LaMoure, {Grace L.} and Lanpher, {Brendan C.} and Lanza, {Ian R.} and Lea Latham and Kimberly LeBlanc and Lee, {Brendan H.} and Hane Lee and Roy Levitt and Lewis, {Richard A.} and Lincoln, {Sharyn A.} and Pengfei Liu and Liu, {Xue Zhong} and Nicola Longo and Loo, {Sandra K.} and Joseph Loscalzo and Maas, {Richard L.} and John MacDowall and Macnamara, {Ellen F.} and MacRae, {Calum A.} and Maduro, {Valerie V.} and Mak, {Bryan C.} and Malicdan, {May Christine V.} and Mamounas, {Laura A.} and Manolio, {Teri A.} and Rong Mao and Kenneth Maravilla and Markello, {Thomas C.} and Ronit Marom and Gabor Marth and Martin, {Beth A.} and Martin, {Martin G.} and Mart{\'i}nez-Agosto, {Julian A.} and Shruti Marwaha and Jacob McCauley and Allyn McConkie-Rosell and McCray, {Alexa T.} and Elisabeth McGee and Heather Mefford and Merritt, {J. Lawrence} and Ghayda Mirzaa and Eva Morava and Moretti, {Paolo M.} and Stephen Pak and Timothy Schedl and Jimann Shin and Lilianna Solnica-Krezel and Jennifer Wambach",
note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",
year = "2022",
month = jan,
doi = "10.1126/sciadv.abl5613",
language = "English",
volume = "8",
journal = "Science Advances",
issn = "2375-2548",
number = "3",
}