Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain
NATURE NEUROSCIENCE
Authors: Anton, ES; Ghashghaei, HT; Weber, JL; McCann, C; Fischer, TM; Cheung, ID; Gassmann, M; Messing, A; Klein, R; Schwab, MH; Lloyd, KCK; Lai, C
Abstract
Neural progenitor proliferation, differentiation and migration are continually active in the rostral migratory stream of the adult brain. Here, we show that the receptor tyrosine kinase ErbB4 is expressed prominently by the neuroblasts present in the subventricular zone and the rostral migratory stream. The neuregulins (NRG1-NRG3), which have been identified as ErbB4 ligands, are detected either in the stream or in adjacent regions. Mice deficient in ErbB4 expressed under the control of either the nestin or the hGFAP promoter have altered neuroblast chain organization and migration and deficits in the placement and differentiation of olfactory interneurons. These findings suggest that ErbB4 activation helps to regulate the organization of neural chains that form the rostral migratory stream and influences the differentiation of olfactory interneuronal precursors.
Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients
PHARMACOGENOMICS JOURNAL
Authors: Taylor, John C.; Bongartz, Tim; Massey, Jonathan; Mifsud, Borbala; Spiliopoulou, Athina; Scott, Ian C.; Wang, Jianmei; Morgan, Michael; Plant, Darren; Colombo, Marco; Orchard, Peter; Twigg, Sarah; McInnes, Iain B.; Porter, Duncan; Freeston, Jane E.; Nam, Jackie L.; Cordell, Heather J.; Isaacs, John D.; Strathdee, Jenna L.; Arnett, Donna; de Hair, Maria J. H.; Tak, Paul P.; Aslibekyan, Stella; van Vollenhoven, Ronald F.; Padyukov, Leonid; Bridges, S. Louis; Pitzalis, Costantino; Cope, Andrew P.; Verstappen, Suzanne M. M.; Emery, Paul; Barnes, Michael R.; Agakov, Felix; McKeigue, Paul; Mushiroda, Taisei; Kubo, Michiaki; Weinshilboum, Richard; Barton, Anne; Morgan, Ann W.; Barrett, Jennifer H.
Abstract
Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genomewide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p =10(-7) for change in DAS28). Some support was also seen for association with ZM/Z/, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.
COA
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