Possible genetic link behind schizophrenia identified
Washington: A gene called Disc1 (Disrupted-In-Schizophrenia 1) may be responsible for causing Schizophrenia, according to two new studies.
Led by Dr. Jill Morris and colleagues at Northwestern University``s Feinberg School of Medicine, both studies have focused on the role of Disc1 in development, particularly the migration of cells to their proper location in the brain and subsequent differentiation into their intended fate.
During development, cells need to properly migrate to their final destination in order to develop into the appropriate cell-type, integrate into the corresponding network of cells and function properly.
Disruption of cell migration can lead to inappropriate cell development and function, resulting in disease.
In the first paper, the researchers followed the role of Disc1 in cranial neural crest (CNC) cells, which are multi-potent cells that give rise to multiple cell types including craniofacial cartilage and the peripheral nervous system during development.
The researchers determined that Disc1 regulates two stem cell maintenance factors that have many functions in CNC cells, including the maintenance of precursor pools, timing of migration onset and the induction of cell differentiation.
The authors showed that Disc1 disruption results in increased expression of these factors, leading to hindered cell migration and a change in cell fate.
"This research indicates that Disc1 may be involved in regulating stem cells and their fate," said Morris.
In the second paper, the researchers studied the hippocampus, a brain area that is involved in learning and memory, and is also associated with the pathology of schizophrenia.
Disc1 is highly expressed in the hippocampus, particularly the dentate gyrus, which is considered the gateway to the hippocampus.
During the study, the researchers decreased Disc1 expression using RNA interference in the developing mouse hippocampus.
They observed that the loss of Disc1 resulted in hindered migration of dentate gyrus granule cells to their proper location in the brain.
"Improper migration of hippocampal neurons may result in altered connectivity in the brain," said Morris.
The first study has been published in the latest online issue of the journal Development, and the second one in Human Molecular Genetics.