The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division.
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/Galphai 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.
Bonaccorsi
Silvia
S
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Genetica e Biologia Molecolare, Università di Roma La Sapienza, P.le A. Moro 5, 00185 Roma, Italy.
Mottier
Violaine
V
Giansanti
Maria Grazia
MG
Bolkan
Bonnie J
BJ
Williams
Byron
B
Goldberg
Michael L
ML
Gatti
Maurizio
M
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010580:Peutz-Jeghers Syndrome / Q000235:genetics / Q000503:physiopathology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; D011494:Protein Kinases; C495775:LKB1 protein, Drosophila; D000091162:AMP-Activated Protein Kinase Kinases