title: Evidence for tangential migration disturbances in human lissencephaly resulting from a defect in LIS1, DCX and ARX genes.
abstract: During corticogenesis, neurons adopt different migration pathways to reach their final position. The precursors of pyramidal neurons migrate radially, whereas most of the GABA-containing interneurons are generated in the ventral telencephalon and migrate tangentially into the neocortex. Then, they use a radial migration mode to establish themselves in an inside-out manner in the neocortex, similarly to pyramidal neurons. In humans, the most severe defects in radial migration result in lissencephaly. Lately, a few studies suggested that lissencephaly was also associated with tangential neuronal migration deficits. In the present report, we investigated potential anomalies of this migration mode in three agyric/pachygyric syndromes due to defects in the LIS1, DCX and ARX genes. Immunohistochemistry was performed on paraffin-embedded supra- and infratentorial structures using calretinin, calbindin and parvalbumin antisera. The results were compared with age-matched control brain tissue. In the Miller-Dieker syndrome, GABAergic neurons were found both in upper layers of the cortex and in heterotopic positions in the intermediate zone and in ganglionic eminences. In the DCX mutant brain, few interneurons were dispersed in the cortical plate, with a massive accumulation in the intermediate zone and subventricular zone as well as in the ganglionic eminences. In the ARX-mutated brain, the cortical plate contained almost exclusively pyramidal cells and was devoid of interneurons. The ganglionic eminences and basal ganglia were poorly cellular, suggesting an interneuron production and/or differentiation defect. These data argue for different mechanisms of telencephalic tangential migration impairment in these three agyric/pachygyric syndromes.
authors.affiliation: Pathology Laboratory, Pole Pathologie-Biologie, Brest University Hospital, Brest, France. pascale.marcorelles@chu-brest.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.forename: Christine
authors.initials: C
authors.lastname: Adde-Michel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: Chérif
authors.initials: C
authors.lastname: Beldjord
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Friocourt
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000172:deficiency*; D001344:Autopsy; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D064032:Calbindin 2; D064026:Calbindins; D016022:Case-Control Studies; D002465:Cell Movement / Q000235:genetics*; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018398:Homeodomain Proteins; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008869:Microtubule-Associated Proteins / Q000172:deficiency*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009479:Neuropeptides / Q000172:deficiency*; D010320:Parvalbumins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency*; D014746:Vimentin / Q000378:metabolism
chemical_list: C469264:ARX protein, human; C576764:CALB2 protein, human; D064032:Calbindin 2; D064026:Calbindins; C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D014157:Transcription Factors; D014746:Vimentin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human