Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS.

Slit1 is a secreted axon guidance molecule, also involved in adult neurogenesis. In physiological conditions, Slit1 loss promotes ectopic dispersal of SVZ-derived neural precursors (SVZ-NPCs) into periventricular structures such as the corpus callosum. Demyelination of the corpus callosum triggers SVZ-NPC migration to ectopic locations and their recruitment by the lesion, suggesting a possible role for Slit1 in SVZ-NPCs ectopic dispersal regulation in pathological conditions. Here, we have investigated the function of Slit1 protein in the recruitment of SVZ-NPCs after CNS demyelination. We find that the dynamics of oligodendrogenesis and temporal profile of developmental myelination in Slit1 -/- mice are similar to Slit1 +/- controls. SVZ micro-dissection and RT-PCR from wild-type mice, show that Slits and Robos are physiologically regulated at the transcriptional level in response to corpus callosum demyelination suggesting their role in the process of SVZ-NPC ectopic migration in demyelinating conditions. Moreover, we find that the number of SVZ-NPCs recruited by the lesion increases in Sli1-/- mice compared to Slit1 +/- mice, leading to higher numbers of Olig2+ cells within the lesion. Time-lapse video-microscopy of immuno-purified NPCs shows that Slit1-deficient cells migrate faster and make more frequent directional changes than control NPCs, supporting a cell-autonomous mechanism of action of Slit1 in NPC migration. In conclusion, while Slit1 does not affect the normal developmental process of oligodendrogenesis and myelination, it regulates adult SVZ-NPC ectopic migration in response to demyelination, and consequently oligodendrocyte renewal within the lesion.

Linguistic profile of individuals with Down syndrome: comparing the linguistic performance of three developmental disorders.

An increasing number of studies, addressing the linguistic abilities of individuals with Down syndrome (DS) suggest that they exhibit strengths and weaknesses within the linguistic domain. This article critically reviews the literature on the linguistic profile of individuals with DS, with particular emphasis on the expression and reception of vocabulary and grammar, including nonverbal linguistic expression during infant development. In doing so, attention is given to recent comparative studies of the linguistic abilities of individuals with DS, Specific Language Impairment (SLI), and Williams syndrome (WS). The possibility that deficits in one cognitive system may have consequences in another cognitive system, and that these consequences may define the nature of the impairment in each clinical syndrome is further discussed with suggestions for future research.

Expressive and receptive vocabulary in children with Williams and Down syndromes.

BACKGROUND: Williams (WS) and Down syndromes (DS) are two genetic disorders that involve intellectual disability (ID) and have been extensively studied over the past decades because of the unique linguistic profiles they exhibit. Recent investigations seek to explore the fractionation of linguistic components within the cognitive system using genetically based neurodevelopmental disorders such as WS and DS and to identify different profiles of linguistic function in these two groups of individuals. METHOD: The 'expressive vocabulary', 'receptive vocabulary', 'word opposites' and 'word definitions' subtests (Level 1) of the Test of Word Knowledge (TOWK) were used to assess lexical skills in six children with WS and five children with DS. RESULTS: Our findings indicate that the two syndromes exhibit substantial differences on linguistic tasks with individuals with WS performing at a higher level compared to those with DS and producing atypical responses in word definitions. The pattern of errors for each syndrome is qualitatively different suggesting that their underlying linguistic mechanisms are distinctive even though ID is similar. CONCLUSIONS: This study supports the differential outcome of two chromosomal disorders with similar ID. It also argues in favour of the large within group variability of the two syndromes that is not related to mental age but rather to different underlying mechanisms supporting language. These findings are discussed in the light of the current evidence concerning linguistic knowledge of neurodevelopmental and genetic disorders.