(Great Neck, N.Y. - July 16, 2009) — Jill A. Morris, Ph.D., the recipient of a 2005 NARSAD Young Investigator Award, is the lead author of two recent studies providing new insight into the role played by the DISC-1 (Disrupted-in-Schizophrenia 1) gene in the process of neurodevelopment and pathogenesis of schizophrenia.
Dr. Morris is an assistant professor in the Program in Human and Molecular Genetics in the department of pediatrics of Northwestern University’s Feinberg School of Medicine and Children's Memorial Research Center.
The hippocampus is an area of the brain that has displayed structural and functional abnormalities in many schizophrenia patients. DISC-1, a well-documented schizophrenia-susceptibility gene, is strongly expressed in the hippocampus from its early development through adulthood.
In an article in the journal Human Molecular Genetics, published online on June 5, Dr. Morris and her colleagues reported evidence from research with genetically altered mice to support the idea that DISC-1 abnormalities may contribute to the onset of schizophrenia through influences on hippocampal development; specifically, by hindering the migration of nerve cells called granule cells in a region of the hippocampus called the dentate gyrus.
The authors state that these spatially-defined differences demonstrate that DISC-1 plays a complex role in the regulation of neuronal migration within the developing brain. Their findings also suggest that DISC-1 disruptions may be conferring an increased risk for schizophrenia through their early influences on the functional connectivity of the hippocampus.
In a second paper, published online July 1 in the journal Development, Dr. Morris and colleagues describe the results of DISC-1 research using the zebrafish as their model and showing that alterations of DISC-1 result in alterations in the expression of two transcription factors, foxd3 and sox10, involved in the maintenance of neural stem cells.
Transcription factors are molecules that affect gene regulation. Neural crest cells are cells that migrate during an early process in nervous-system development. While they function to form most of the peripheral nervous system, these cells share characteristics with cells of the developing brain, including reliance on a common subset of transcription factors regulating cellular differentiation and responsiveness to extracellular signals.
The authors write: “Although this study highlights the role of DISC-1 in the neural crest, it provides insight into a basic cellular function of this protein in transcription factor regulation that might be preserved in the central nervous system. Foxd3 is a well-characterized marker of stem cells expressed in neurogenic regions of the rodent brain.”
They conclude: “Understanding the basic functions of DISC-1 in transcriptional regulation, cell migration and cell differentiation in the zebrafish neural crest might give insight into the cellular processes that, when disrupted, predispose individuals to mental illness.”
Link to article: http://www.narsad.org/news/press/rg_2009/res20090716.html