About ZEBrA

Our Goal

For decades, songbirds have served as a premier model for conducting neurobiological research with wide implications for understanding human health and disease. Recently, a series of NINDS-, NHGRI- and NIGMS-funded projects has made available a large collection of modern molecular and genomic tools and resources that have begun to shed light on the basic molecular and genetic mechanisms that regulate the song control system and singing behavior. These resources include normalized brain cDNA libraries, comprehensive annotated brain EST databases, a BAC library, and the completion of the sequencing, assembly and annotation of the zebra finch genome. An important next step towards making full use of these resources and for understanding how genes relate to brain function and behavior in songbirds is to map gene expression in the context of functional brain circuits. The goal of the ZEBrA project is to develop a publically available on-line digital atlas that documents the expression of a large collection of genes within the brain of adult male zebra finches.

The Atlas

ZEBrA is being constructed in the Mello laboratory (Dept. of Behavioral Neuroscience, OHSU, Portland OR). Genes are typically referenced by their name (i.e. Gene Symbols), established and curated by the Human Genome Nomenclature Consortium (HGNC). All of the clones used for this project are derived from normalized zebra finch brain cDNA libraries and can be obtained through the University of Illinois (Songbird:ESTIMA clone collection). DIG-labeled antisense riboprobes are hybridized to parasagittal brain sections derived from adult male zebra finches using an optimized non-radioactive in situ hybridization protocol, specifically developed for ZEBrA. Genes with highly differential expression patterns are hybridized to an Atlas Series (5-9 levels, ~0.2 - 4.0 mm from midline), while genes with non-differential patterns are hybridized to a Subset Series (1-4 levels, ~1.0 and 2.4 mm from midline) focusing on documenting expression in song nuclei; all brains are from confirmed awake non-singing birds. Sections are imaged with a digital scanner (Olympus Nanozoomer) by the Mitra lab at Cold Spring Harbor Laboratory. Images are presented with a set of corresponding atlas drawings derived from a histological atlas of the zebra finch brain developed by Drs. Harvey Karten and Partha Mitra.

The Genes

ZEBrA includes various sets of genes that are of relevance to birdsong neurobiology identified through microarray screenings, as well as others that represent efforts to cover important gaps in our understanding of the molecular and neurochemical properties of the song control system, clarify relationships between avian and mammalian brains, and address other specific needs from the songbird and avian brain research communities. The main categories are:

(1) Molecular Markers of the Song System. These genes were identified through microarray screening and deep sequencing efforts as being differentially expressed in song nuclei compared to adjacent brain areas, and thus represent molecular specializations that define unique properties of the song system. These genes are also neuroanatomical markers that help to define nuclear boundaries, allowing greater precision in studies of nuclear size, shape or organization that occur naturally or as a result of experimental manipulations. ZEBrA will include several hundred genes that are markers of the major telencephalic song nuclei (HVC, LMAN, RA and area X). Use the Neuroanatomical Marker Browser to quickly retrieve these genes

(2) - Physiological Processes of Relevance to Birdsong. These genes and gene families are known from studies in other organisms to play key roles in various aspects of brain function, including neuronal excitability (e.g., neurotransmitter/neuromodulator markers and receptors, ion channels, regulators of synaptic function), hormone action (e.g., hormone synthetic enzymes and receptors), gene regulation (transcription factors) and cell cycle control (e.g. growth and neurotrophic factors and receptors, cell division modulators, apoptosis markers), all representing major areas of research in songbirds. ZEBrA will eventually include several hundred such genes. Use the Gene Family Browser to quickly retrieve these genes.
(3) - Genes of Comparative Relevance. We are selecting a large collection of genes representing the zebra finch orthologs of markers that are selectively or differentially expressed in different parts of the mammalian brain (e.g., markers of different cortical layers, amygdalar nuclei, hippocampal subdivisions, etc). Inclusion of these genes in ZEBrA will help to shed light on similarities and differences in the organization of mammalian and avian brains. Specifically, this analysis will help determine the extent to which molecular specializations of homologous brain structures are shared between mammals and birds, and provide further insights into the relatedness of regions whose homologies are contentious. Use the Neuroanatomical Marker Browser to quickly retrieve these genes

Funding for Project ZEBrA

Project ZEBrA was initially funded by a pilot grant from the NIH/NINDS (R03-NS059755) and is currently funded by a resource grant from the NIH/NIGMS (Grant# R24 GM092842-02) to CVM.

Team ZEBrA (Mello lab)

Claudio V. Mello - Principal Investigator
Peter V. Lovell - Lead ZEBrA Developer and Project Manager
Brian R. Snider - Lead Programmer, Database Management
Morgan Wirthlin - in situ Pipeline, Image processing, Database management
Julia Carleton - Former team member
Tessa Marzulla - Former team member
Anne McHugh - Former team member
Katy Horback - Former team member
Michelle Hribar - Former Programmer and Project Consultant

ZEBrA Marker Annotators

Claudio Mello
Peter Lovell
Morgan Wirthlin

Imaging (Mitra lab)

Partha Mitra - Project consultant, Imaging resource
Vadim Pinskiy - Imaging Coordinator
Alex Tolpygo - Imaging Coordinator

Project Consultants

David F. Clayton - UIUC
Anton J. Reiner - UTHSC
Harvey J. Karten - UCSD

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