Biomedical subjects

Jenny Gunnersen

Publications and source records attributed to Jenny Gunnersen.

5 recordsLinked to original sources

PubMed2006

Nedd4-WW domain-binding protein 5 (Ndfip1) is associated with neuronal survival after acute cortical brain injury.

Understanding the transcriptional response to neuronal injury after trauma is a necessary prelude to formulation of therapeutic strategies. We used Serial Analysis of Gene Expression (SAGE) to identify 50,000 sequence tags representing 18,000 expressed genes in the cortex 2 h after traumatic brain injury (TBI). A similar tag library was obtained from sham-operated cortex. The SAGE data were validated on biological replicates using quantitative real-time-PCR on multiple samples at 2, 6, 12, and 24 h after TBI. This analysis revealed that the vast majority of genes showed a downward trend in their pattern of expression over 24 h. This was confirmed for a subset of genes using in situ hybridization and immunocytochemistry on brain sections. Of the overexpressed genes in the trauma library, Nedd4-WW (neural precursor cell expressed, developmentally downregulated) domain-binding protein 5 (N4WBP5) (also known as Ndfip1) is strongly expressed in surviving neurons around the site of injury. Overexpression of N4WBP5 in cultured cortical neurons increased the number of surviving neurons after gene transfection and growth factor starvation compared with control transfections. These results identify N4WBP5 as a neuroprotective protein and, based on its known interaction with the ubiquitin ligase Nedd4, would suggest protein ubiquitination as a possible survival strategy in neuronal injury.

Acute Disease↗

PubMed2006

Layer positioning of late-born cortical interneurons is dependent on Reelin but not p35 signaling.

We tested the response of interneurons to the absence of Reelin signaling or p35 in the mouse neocortex. We provide three independent strands of evidence to demonstrate that layering of late-born (but not early-born) interneurons is regulated by Reelin signaling. First, early-born and late-born interneurons behaved differently in mice lacking Reelin or disabled 1 (Dab1). Early-born interneurons showed layer inversion, whereas late-born interneurons did not demonstrate layer inversion but were randomly distributed across the cortex. Second, in p35 mutant brains (in which Reelin signaling is intact), late-born interneurons are appropriately positioned in the upper layers despite the malpositioning of all other cortical neurons in these mice. Third, transplanted late-born interneuron precursors (wild type) into Dab1(-/-) cortices showed appropriate upper layer segregation. Together, these results indicate that, in the absence of Reelin signaling, late-born interneurons fail to laminate properly, and this is restored in an environment in which Reelin signaling is intact. These studies suggest different mechanisms for the stratification of cortical interneurons. Whereas the early-born interneurons appear to be associated with projection neuron layering, late-born interneurons rely on Reelin signaling for their correct lamination.

Animals↗

PubMed2004

A comparative analysis of transcribed genes in the mouse hypothalamus and neocortex reveals chromosomal clustering.

The hypothalamus and neocortex are subdivisions of the mammalian forebrain, and yet, they have vastly different evolutionary histories, cytoarchitecture, and biological functions. In an attempt to define these attributes in terms of their genetic activity, we have compared their genetic repertoires by using the Serial Analysis of Gene Expression database. From a comparison of 78,784 hypothalamus tags with 125,296 neocortical tags, we demonstrate that each structure possesses a different transcriptional profile in terms of gene ontological characteristics and expression levels. Despite its more recent evolutionary history, the neocortex has a more complex pattern of gene activity. Gene identities and levels of gene expression were mapped to their chromosomal positions by using in silico definition of GC-rich and GC-poor genome bands. This analysis shows contrasting views of gene activity on a genome scale that is unique to each brain substructure. We show that genes that are more highly expressed in one tissue tend to be clustered together on a chromosomal scale, further defining the genetic identity of either the hypothalamus or neocortex. We propose that physical proximity of coregulated genes may facilitate transcriptional access to the genetic substrates of evolutionary selection that ultimately shape the functional subdivisions of the mammalian brain.

Animals↗

PubMed2002

Region-specific expression of the helix-loop-helix gene BETA3 in developing and adult brains.

Members of the basic helix-loop-helix (bHLH) transcription factor family are crucial regulators of neuronal cell generation and cell fate. A number of bHLH genes are expressed in the developing cerebral cortex, including MASH-1, neurogenin2 and NeuroD implying the existence of a regulatory and possibly redundant network of family members. BETA3 is a novel member originally cloned from pancreatic cells but we report here highly restricted expression patterns in developing forebrain structures that are highly stage-specific. We show that BETA3 mRNA is found in both neocortex and archicortex, mainly in cells that have reached their migratory destinations but is largely absent from proliferative zones. These expression data would suggest that BETA3 function is linked to the establishment rather than the initiation of neuronal fates.

Animals↗

PubMed2002

Global gene expression analysis of developing neocortex using SAGE.

The mammalian brain is estimated to contain about a hundred billion neurons, making it the most complex biological structure on earth. Trying to understand the assembly and function of this elaborate organ is a formidable task. Yet the information to build a brain is encoded by no more than a subset of the 80,000 genes present in the genome, a more manageable number. This review describes the use of SAGE technology (Serial Analysis of Gene Expression) to decode the genetic repertoire of genes that are differentially expressed in time and in space during development of the neocortex, the part of the mammalian brain responsible for complex traits. We demonstrate that SAGE is not only powerful for generating comprehensive molecular portraits from the developing cortex but can also assist in discovering new genes.

Animals↗