Branching and nucleokinesis defects in migrating interneurons derived from doublecortin knockout mice.
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.
Département de Génétique et Développement, Institut Cochin, F-75014 Paris, France.
Caroline
C
Kappeler
Yoann
Y
Saillour
Jean-Pierre
JP
Baudoin
Françoise Phan Dinh
FP
Tuy
Chantal
C
Alvarez
Christophe
C
Houbron
Patricia
P
Gaspar
Ghislaine
G
Hamard
Jamel
J
Chelly
Christine
C
Métin
Fiona
F
Francis
D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D007395:Interneurons / Q000473:pathology*; D008297:Male; D008473:Median Eminence / Q000166:cytology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D009924:Organ Culture Techniques
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides