@article{97ded48b768c433ba2d792f6f3a9f5c6,
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 Surendra Dasari and Lanpher, {Brendan C.} and Lanza, {Ian R.} and Eva Morava and Devin Oglesbee",
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 (US)",
volume = "8",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "3",
}