Defective Neurogenesis in Citron Kinase Knockout Mice by Altered Cytokinesis and Massive Apoptosis

AbstractCitron-kinase (Citron-K) has been proposed by in vitro studies as a crucial effector of Rho in regulation of cytokinesis. To further investigate in vivo its biologic functions, we have inactivated Citron-K gene in mice by homologous recombination. Citron-K−/− mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with depletion of specific neuronal populations. These abnormalities arise during development of the central nervous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in specific neuronal precursors. Moreover, they suggest a novel molecular mechanism for a subset of human malformative syndromes of the CNS

A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (∼660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in a postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. This second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotype

L'AVVENTURA DELLA LINGUA: MARIA LUISA ALTIERI BIAGI FRA RICERCA E DIDATTICA: PRESENTAZIONE di Silvia Morgana

Gli allievi di Maria Luisa Altieri Biagi ripercorrono in tre articoli il suo lungo impegno teorico e civile per l’educazione linguistica e la formazione degli insegnanti. Angela Chiantera e Cristiana De Santis analizzano le sue molteplici esperienze per il rinnovamento della didattica linguistica nella stretta connessione tra lingua e pensiero. Francesca Gatta ne illustra gli studi sulla letteratura contemporanea e le analisi del testo letterario in prospettiva di educazione linguistica, mentre Fabio Atzori evidenzia i rapporti tra i suoi fondamentali studi sulla lingua scientifica e la sua produzione per la scuola.   The adventure of language: Maria Luisa Altieri Biagi from research to teaching The students of Maria Luisa Altieri Biagi review her long-standing theoretical and civil commitment to language education and teacher training in three articles. Angela Chiantera and Cristiana De Santis analyze her multiple efforts to renew language teaching with focus on the close connection between language and thought. Francesca Gatta illustrates her studies on contemporary literature and the analysis of the literary text in the perspective of language education, while Fabio Atzori highlights the relationship between her fundamental studies on scientific language and her production for schools