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A gene expression atlas of the central nervous system based on bacterial artificial chromosomes

Abstract

The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.

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Figure 1: Expression of Chat from different BAC constructs.
Figure 2: Cell lineage revealed by expression data from reporter gene analysis in BAC transgenic mice.
Figure 3: Predicting developmental functions for specific genes on the basis of expression data in BAC transgenic mice.
Figure 4: Genesis and migration of cortical interneurons is revealed with Lhx6 BAC transgenic mice.
Figure 5: Expression of Pde1c reveals a novel and distinct migratory pathway in developing brain.
Figure 6: Layer-specific gene expression in the developing cerebral cortex.
Figure 7: Cell-specific EGFP marker expression in the adult striatum of BAC transgenic mice.

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Acknowledgements

We are grateful to the staff of GENSAT who generated this data, including C. Grevstad, A. Sung, P. Dyer, H. Zhu, S. M. Ehta, C. Wang, T. Allanson, C. Madden, Y. Huang, H. Sherman and H. Feng; to N. Adams who helped to write the macros for the image-acquisition system and who provided advice on histological methods; to D. Birchfield and B. Dittmer-Roche who helped to write the database programs; and to J. Walsh who helped with the preparation of the manuscript. The GENSAT project is supported by grants from the National Institutes of Health. N.H. and A.J. are investigators of the Howard Hughes Medical Institute.

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Correspondence to Mary E. Hatten or Nathaniel Heintz.

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Gong, S., Zheng, C., Doughty, M. et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425, 917–925 (2003). https://doi.org/10.1038/nature02033

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