Neuronal differentiation is characterized by changes in both the extent of intercellular coupling and the expression patterns of connexin genes that encode gap junction proteins. Using a neuroblastoma culture system, we have found that stable exogenous expression of different gap junction genes results in either retarded or accelerated response to differentiating agents. Comparing gene expression using locally produced cDNA microarrays indicates candidate genes whose expression is enhanced or depressed in the transfected neuroblastoma cells. However, the preliminary studies raise important questions regarding the technique, including threshold of detection, reliability for each of the spots in the array and detection of clusters representing gene expression patterns.
The Specific Aims of this application are to apply mathematical algorithms and modify experimental techniques so as to: 1) minimize the spot ratio errors; 2) determine expected values and controllable fluctuations of gene expression; 3) build the pre-Hilbert space of standard gene expression (SSGE); 4) compute the so-called """"""""pathologs"""""""" of gene expression for parental and transfected cells; and 5) define gene clusters within the SSGE. We expect that these studies will not only improve our use of the microarray analysis, but will develop new concepts by which such expression patterns are generally used.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS042807-01
Application #
6423596
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Leblanc, Gabrielle G
Project Start
2001-09-27
Project End
2003-07-31
Budget Start
2001-09-27
Budget End
2002-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$209,219
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Iacobas, Dumitru A; Iacobas, Sanda; Spray, David C (2007) Connexin43 and the brain transcriptome of newborn mice. Genomics 89:113-23
Dobrenis, K; Chang, H-Y; Pina-Benabou, M H et al. (2005) Human and mouse microglia express connexin36, and functional gap junctions are formed between rodent microglia and neurons. J Neurosci Res 82:306-15
Iacobas, Dumitru A; Iacobas, Sanda; Li, W E I et al. (2005) Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart. Physiol Genomics 20:211-23
Iacobas, Dumitru A; Scemes, Eliana; Spray, David C (2004) Gene expression alterations in connexin null mice extend beyond the gap junction. Neurochem Int 45:243-50
Iacobas, Dumitru A; Urban-Maldonado, Marcia; Iacobas, Sanda et al. (2003) Array analysis of gene expression in connexin-43 null astrocytes. Physiol Genomics 15:177-90
Mukherjee, Shankar; Belbin, Thomas J; Spray, David C et al. (2003) Microarray analysis of changes in gene expression in a murine model of chronic chagasic cardiomyopathy. Parasitol Res 91:187-96
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Iacobas, D A; Urban, Marcia; Iacobas, Sanda et al. (2002) Transcriptomic characterization of four classes of cell-cell/cell-matrix genes in brains and hearts of wild type and connexin43 null mice. Rom J Physiol 39-40:91-116
Iacobas, D A; Urban, Marcia; Iacobas, Sanda et al. (2002) Control and variability of gene expression in mouse brain and in a neuroblastoma cell line. Rom J Physiol 39-40:71-90