Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons.
Recently, we and others reported that the doublecortin gene is responsible for X-linked lissencephaly and subcortical laminar heterotopia. Here, we show that Doublecortin is expressed in the brain throughout the period of corticogenesis in migrating and differentiating neurons. Immunohistochemical studies show its localization in the soma and leading processes of tangentially migrating neurons, and a strong axonal labeling is observed in differentiating neurons. In cultured neurons, Doublecortin expression is highest in the distal parts of developing processes. We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. Our data suggest that the cortical dysgeneses associated with the loss of Doublecortin function might result from abnormal cytoskeletal dynamics in neuronal cell development.
Francis
F
F
U129 de l'INSERM, Institut Cochin de Génétique Moléculaire, Paris. ffrancis@infobiogen.fr
Koulakoff
A
A
Boucher
D
D
Chafey
P
P
Schaar
B
B
Vinet
M C
MC
Friocourt
G
G
McDonnell
N
N
Reiner
O
O
Kahn
A
A
McConnell
S K
SK
Berwald-Netter
Y
Y
Denoulet
P
P
Chelly
J
J
D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000096:biosynthesis / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D014404:Tubulin / Q000302:isolation & purification / Q000378:metabolism
C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; D012333:RNA, Messenger; D014404:Tubulin