Editor's Summary
1 June 2006
Down's syndrome
Down's syndrome is caused by an extra chromosome; somehow a 1.5-fold increase in the dosage of a gene or genes on chromosome 21 causes the wide-reaching effects associated with the condition. A study using 'knockout' mice now identifies two genes as candidates for involvement. A 1.5-fold increase in dosage of DSCR1 and DYRK1a destabilizes the regulation of signalling pathways involving the NFAT transcription factor. The discovery follows the surprise finding that NFATc1-4 and calcineurin mutant mice demonstrate nearly all the characteristics of Down's syndrome. In an unrelated paper, a genome-wide RNAi screen reveals conserved regulators of NFAT in Drosophila. NFAT is a purely vertebrate transcription factor, but this work breaks new ground by using Drosophila cells to study the function of a protein artificially introduced from a mammalian species. Pathways regulating the subcellular localization of NFAT proteins are strongly conserved across species and this new approach can identify new regulators of a transcription factor normally expressed in vertebrates.
News and Views: Down's syndrome: Critical genes in a critical region
The NFAT transcription factors activate the expression of many genes involved in the immune response and the development of a variety of tissues. They have now been implicated in Down's syndrome.
Charles J. Epstein
doi:10.1038/441582a
Article: NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21
Joseph R. Arron, Monte M. Winslow, Alberto Polleri, Ching-Pin Chang, Hai Wu, Xin Gao, Joel R. Neilson, Lei Chen, Jeremy J. Heit, Seung K. Kim, Nobuyuki Yamasaki, Tsuyoshi Miyakawa, Uta Francke, Isabella A. Graef & Gerald R. Crabtree
doi:10.1038/nature04678
Abstract | Full Text | PDF (1,047K) | Supplementary information
Letter: A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT
Yousang Gwack, Sonia Sharma, Julie Nardone, Bogdan Tanasa, Alina Iuga, Sonal Srikanth, Heidi Okamura, Diana Bolton, Stefan Feske, Patrick G. Hogan & Anjana Rao
doi:10.1038/nature04631
First paragraph | Full Text | PDF (547K) | Supplementary information
