Branching and nucleokinesis defects in migrating interneurons derived from doublecortin knockout mice

• Published in: Human molecular genetics 2006-05, Vol.15 (9), p.1387-1400
• Main Authors: Kappeler, Caroline, Saillour, Yoann, Baudoin, Jean-Pierre, Tuy, Françoise Phan Dinh, Alvarez, Chantal, Houbron, Christophe, Gaspar, Patricia, Hamard, Ghislaine, Chelly, Jamel, Métin, Christine, Francis, Fiona
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry, Molecular Biology; Biological and medical sciences; Cell Movement - genetics; Cell Nucleus - genetics; Cell Nucleus - metabolism; Cells, Cultured; Coculture Techniques; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Interneurons - pathology; Life Sciences; Male; Median Eminence - cytology; Median Eminence - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins - deficiency; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - physiology; Molecular and cellular biology; Neuropeptides - deficiency; Neuropeptides - genetics; Neuropeptides - physiology; Organ Culture Techniques
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddl062

Type I lissencephaly results from mutations in the doublecortin (DCX) and LIS1 genes. We generated Dcx knockout mice to further understand the pathophysiological mechanisms associated with this cortical malformation. Dcx is expressed in migrating interneurons in developing human and mouse brains. Video microscopy analyses of such tangentially migrating neuron populations derived from the medial ganglionic eminence show defects in migratory dynamics. Specifically, the formation and division of growth cones, leading to the production of new branches, are more frequent in knockout cells, although branches are less stable. Dcx-deficient cells thus migrate in a disorganized manner, extending and retracting short branches and making less long-distant movements of the nucleus. Despite these differences, migratory speeds and distances remain similar to wild-type cells. These novel data thus highlight a role for Dcx, a microtubule-associated protein enriched at the leading edge in the branching and nucleokinesis of migrating interneurons.