@article {203,
	title = {Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors.},
	journal = {Neuron},
	volume = {84},
	year = {2014},
	month = {2014 Dec 17},
	pages = {1226-39},
	abstract = {<p>Exome sequencing analysis of over 2,000 children with complex malformations of cortical development identified five independent (four homozygous and one compound heterozygous) deleterious mutations in KATNB1, encoding the regulatory subunit of the microtubule-severing enzyme Katanin. Mitotic spindle formation is defective in patient-derived fibroblasts, a consequence of disrupted interactions of mutant KATNB1 with KATNA1, the catalytic subunit of Katanin, and other microtubule-associated proteins. Loss of KATNB1 orthologs in zebrafish (katnb1) and flies (kat80) results in microcephaly, recapitulating the human phenotype. In the developing Drosophila optic lobe, kat80 loss specifically affects the asymmetrically dividing neuroblasts, which display supernumerary centrosomes and spindle abnormalities during mitosis, leading to cell cycle progression delays and reduced cell numbers. Furthermore, kat80 depletion results in dendritic arborization defects in sensory and motor neurons, affecting neural architecture. Taken together, we provide insight into the mechanisms by which KATNB1 mutations cause human cerebral cortical malformations, demonstrating its fundamental role during brain development. </p>},
	keywords = {Adenosine Triphosphatases, Animals, Brain, Cell Count, Cell Division, Dendrites, Drosophila, Drosophila Proteins, Humans, Katanin, Mice, Microcephaly, Microtubule-Associated Proteins, Mutation, Neural Stem Cells, Neurogenesis, Optic Lobe, Nonmammalian, Spindle Apparatus, Zebrafish},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2014.12.014},
	author = {Mishra-Gorur, Ketu and {\c C}a{\u g}layan, Ahmet Okay and Schaffer, Ashleigh E and Chabu, Chiswili and Henegariu, Octavian and Vonhoff, Fernando and Akg{\"u}m{\"u}{\c s}, G{\"o}zde Tu{\u g}ce and Nishimura, Sayoko and Han, Wenqi and Tu, Shu and Baran, Bur{\c c}in and G{\"u}m{\"u}{\c s}, Hakan and Dilber, Cengiz and Zaki, Maha S and Hossni, Heba A A and Rivi{\`e}re, Jean-Baptiste and Kayserili, H{\"u}lya and Spencer, Emily G and Rosti, Rasim O and Schroth, Jana and Per, H{\"u}seyin and Caglar, Caner and {\c C}a{\u g}lar, {\c C}a{\u g}ri and D{\"o}len, Duygu and Baranoski, Jacob F and Kumanda{\c s}, Sefer and Minja, Frank J and Erson-Omay, E Zeynep and Mane, Shrikant M and Lifton, Richard P and Xu, Tian and Keshishian, Haig and Dobyns, William B and Chi, Neil C and {\v S}estan, Nenad and Louvi, Angeliki and Bilguvar, Kaya and Yasuno, Katsuhito and Gleeson, Joseph G and G{\"u}nel, Murat}
}
