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The Journal of Neuroscience, August 17, 2005, 25(33):7586-7600; doi:10.1523/JNEUROSCI.0522-05.2005

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Development/Plasticity/Repair
Telencephalic Embryonic Subtractive Sequences: A Unique Collection of Neurodevelopmental Genes

Alessandro Bulfone,² Pietro Carotenuto,^1,3 * Andrea Faedo,^2 * Veruska Aglio,^1 * Livia Garzia,^1,3 Anna Maria Bello,¹ Andrea Basile,² Alessandra Andrè,¹ Massimo Cocchia,³ Ombretta Guardiola,¹ Andrea Ballabio,³ John L. R. Rubenstein,⁴ and Massimo Zollo¹

¹Centro di Ingegneria Genetica e Biotecnologie Avanzate, 80145 Napoli, Italy, ²Stem Cell Research Institute-Hospital San Raffaele, Istituto Scientifico San Raffaele, 20132 Milan, Italy, ³Telethon Institute of Genetics and Medicine, 80131 Naples, Italy, and ⁴Nina Ireland Laboratory of Developmental Neurobiology, Center for Neurobiology and Psychiatry Genetics, University of California at San Francisco, San Francisco, California 94143-2611

The vertebrate telencephalon is composed of many architectonically and functionally distinct areas and structures, with billions of neurons that are precisely connected. This complexity is fine-tuned during development by numerous genes. To identify genes involved in the regulation of telencephalic development, a specific subset of differentially expressed genes was characterized. Here, we describe a set of cDNAs encoded by genes preferentially expressed during development of the mouse telencephalon that was identified through a functional genomics approach. Of 832 distinct transcripts found, 223 (27%) are known genes. Of the remaining, 228 (27%) correspond to expressed sequence tags of unknown function, 58 (7%) are homologs or orthologs of known genes, and 323 (39%) correspond to novel rare transcripts, including 48 (14%) new putative noncoding RNAs. As an example of this latter group of novel precursor transcripts of micro-RNAs, telencephalic embryonic subtractive sequence (TESS) 24.E3 was functionally characterized, and one of its targets was identified: the zinc finger transcription factor ZFP9. The TESS transcriptome has been annotated, mapped for chromosome loci, and arrayed for its gene expression profiles during neural development and differentiation (in Neuro2a and neural stem cells). Within this collection, 188 genes were also characterized on embryonic and postnatal tissue by in situ hybridization, demonstrating that most are specifically expressed in the embryonic CNS. The full information has been organized into a searchable database linked to other genomic resources, allowing easy access to those who are interested in the dissection of the molecular basis of telencephalic development.

Key words: telencephalon; EST; gene array; in situ hybridization; neurodevelopmental; diseases

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Received Feb 8, 2005; revised June 9, 2005; accepted June 10, 2005.

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