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First published online May 16, 2007
doi: 10.1242/10.1242/dev.02848

Development 134, 2183-2193 (2007)
Published by The Company of Biologists 2007
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The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division

Silvia Bonaccorsi1, Violaine Mottier1, Maria Grazia Giansanti1, Bonnie J. Bolkan2, Byron Williams2, Michael L. Goldberg2 and Maurizio Gatti1,*

1 Istituto Pasteur-Fondazione Cenci Bolognetti and Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Genetica e Biologia Molecolare, Università di Roma "La Sapienza", P.le A. Moro 5, 00185 Roma, Italy.
2 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USA.

* Author for correspondence (e-mail: maurizio.gatti{at}uniroma1.it)

Accepted 12 March 2007

We have isolated lethal mutations in the Drosophila lkb1 gene (dlkb1), the homolog of C. elegans par-4 and human LKB1 (STK11), which is mutated in Peutz-Jeghers syndrome. We show that these mutations disrupt spindle formation, resulting in frequent polyploid cells in larval brains. In addition, dlkb1 mutations affect asymmetric division of larval neuroblasts (NBs); they suppress unequal cytokinesis, abrogate proper localization of Bazooka, Par-6, DaPKC and Miranda, but affect neither Pins/G{alpha}i localization nor spindle rotation. Most aspects of the dlkb1 phenotype are exacerbated in dlkb1 pins double mutants, which exhibit more severe defects than those observed in either single mutant. This suggests that Dlkb1 and Pins act in partially redundant pathways to control the asymmetry of NB divisions. Our results also indicate that Dlkb1 and Pins function in parallel pathways controlling the stability of spindle microtubules. The finding that Dlkb1 mediates both the geometry of stem cell division and chromosome segregation provides novel insight into the mechanisms underlying tumor formation in Peutz-Jeghers patients.

Key words: Lkb1, Neuroblasts, Asymmetric division, Spindle formation, Drosophila






© The Company of Biologists Ltd 2007