Transcription profiling of mouse GAP-43 HZ and knockout mouse barrel cortex show modifications in genes associated with synaptogenesis and barrel map formation

ABSTRACT: Mice lacking the growth associated protein, GAP-43, (KO) show multiple deficits in forebrain axon guidance and cortical cell differentiation (Donovan and McCasland, 2005). As a result, GAP-43 KO mice fail to form barrels in mouse somatosensory cortex (S1) (Maier et al., 1999). GAP-43 heterozygous (HZ) mice show abnormalities in axonal pathfinding and show larger than normal barrels in layer IV S1 due to widely branched thalamocortical afferents (TCAs). Regardless of abnormalities during early development, HZ barrels become indistinguishable from WT by postnatal day 26. One explanation for these findings is that compensatory mechanisms may be activated in GAP-43 HZ cortex. We have used mRNA microarray expression analysis to gain a more comprehensive view of genes involved in GAP-43 signaling during barrel map formation. Using laser microdissection , cortical cells of the barrel cortex were excised, RNA extracted and used in GeneChip analysis. Expression profiling and functional gene group analysis of RNA from WT, HZ, and KO cortex at postnatal day 5 was performed. We identified thousands of transcripts differentially expressed across the genotypes. Verification of selected changes in gene expression was accomplished using in situ hybridization. Our results suggest an adaptive modification in transcript expression of genes involved in cell-cell communication and synaptogenesis. These modifications appear important in forward and reverse signaling as well as maintaining synchrony between the cells. Compensatory up- and down regulation of synapse-associated genes may explain the reverse in HZ phenotype from P7 to P26. Moreover, these findings provide new insight into the role GAP-43 plays in several pathways associated with synaptogenesis and trans-synaptic signaling. Experiment Overall Design: 3 replicate RNA samples were prepared from laser microdissected barrel cortex samples of WT, HZ and KO mice at a single timepoint (postnatal day 5)

ORGANISM(S): Mus musculus

SUBMITTER: Frank Middleton 

PROVIDER: E-GEOD-12687 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress