期刊
NEURON
卷 84, 期 6, 页码 1240-1257出版社
CELL PRESS
DOI: 10.1016/j.neuron.2014.12.017
关键词
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资金
- NIH NINDS [F31NS083111, R01NS035129]
- NIH NIGMS [T32GM007753, R01GM095941]
- NIH NHLBI [T32HL007731]
- Manton Center for Orphan Disease Research
- F. Hoffman-La Roche Ltd.
- Clinical Investigator Training Program at Harvard-MIT Health Sciences and Technology
- BIDMC
- Pfizer, Inc.
- Merck Company, Inc
- Nancy Lurie Marks Junior Faculty MeRIT Fellowship
- Leonard and Isabelle Goldenson Research Fellowship
- KACST [09-MED941-20]
- NIH NIAMS [R01AR054396]
- Burroughs Wellcome Fund
- Packard Foundation
- Sandler Family Supporting Foundation
- Strategic Positioning Fund for Genetic Orphan Diseases
- A*STAR Investigatorship from the Agency for Science, Technology and Research in Singapore
- A*STAR
- EMBO
- NIH NIDCR [1U01DE024434-01]
- BCH Orthopedic Surgical Foundation
- NIH NIMH [RC2MH089952]
- Qatar National Research Fund National Priorities Research Program
Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development.
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