Jill Morris, PhD Assistant Professor Pediatrics, CMRC Molecular basis of schizophrenia Curricula: Developmental Biology Molecular Biology and Genetics Neurobiology E-mail:   j-morris4@northwestern.edu

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Schizophrenia is a devastating neurodevelopmental illness, which affects 1% of the population and is associated with high rates of morbidity and mortality.  We focus our research on the cellular mechanisms by which DISC1, a schizophrenia susceptibility gene, affects neurodevelopment. DISC1 was initially identified in a large Scottish family with members who suffered from schizophrenia, bipolar disorder and recurrent major depression. DISC1’s association with schizophrenia has been confirmed in other population and family studies. Genetic studies have also indicated a DISC1 association with bipolar affective disorder and with autism and Asperger syndrome. Understanding the genetic and developmental basis of schizophrenia is critical for discovering treatments. 

Two recent publications by the Morris laboratory focus 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.

The first paper (Drerup CM, Wiora HM, Topczewski J, Morris JA. Development, 2009, 136:2623-2632) followed the role of Disc1 in cranial neural crest (CNC) cells using zebrafish.  CNC cells are multi-potent cells that give rise to multiple cell types including craniofacial cartilage and the peripheral nervous system during development.  They also are similar to neurons in their high mobility, response to signals and cellular origin.  We 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.  We demonstrated that Disc1 disruption results in increased expression of these factors, leading to hindered cell migration and a change in cell fate. 

The second paper (Meyer KD, Morris JA. Hum Mol Genet, 2009, 18(17): 3286-3297) 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.  In this study, we decreased Disc1 expression using RNA interference in the developing mouse hippocampus.  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.   

Selected Publications:

Drerup CM, Wiora HM, Topczewski J, Morris JA (2009) Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation. Development. 136(15):2623-32. Epub 2009 Jul 1.

Meyer KD, Morris JA (2009) Disc1 regulates granule cell migration in the developing hippocampus. Hum Mol Genet. 18(17):3286-97. Epub 2009 Jun 5.

Meyer KD, Morris JA (2008) Immunohistochemical analysis of Disc1 expression in the developing and adult hippocampus. Gene Expr Patterns. 8(7-8):494-501. Epub 2008 Jun 24.

Drerup CM, Ahlgren SC, Morris JA. (2007) Expression profiles of ndel1a and ndel1b, two orthologs of the NudE-Like gene, in the zebrafish. Gene Expr Patterns. 7(6):672-679. Epub 2007 Mar 30.

Austin, C.P., Ky, B., Ma, L., Morris, J.A., Shughrue, P.J.  (2004) Expression of Disc1, a schizophrenia associated gene, is predominant in the hippocampus throughout development.  Neuroscience, 124 (1), 3-10.

Austin CP, Ky B, Ma L, Morris JA and Shughrue PJ.  DISC1 (Disrupted-In-Schizophrenia 1) is Expressed in Limbic Regions of the Primate Brain.  NeuroReport 2003 May 23;14(7):951-4.

Ma, L., Liu, Y., Ky, B., Shughrue, P.J., Austin, C.P. and Morris, J.A. (2002) Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1). Genomics, 80, 662-672.

Millar, J.K., Wilson-Annan, J.C., Anderson, S., Christie, S., Taylor, M.S., Semple, C.A., Devon, R.S., Clair, D.M., Muir, W.J.,  et al. (2000) Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum. Mol. Genet., 9, 1415-1423.

Morris, J.A., Kandpal, G., Ma, L., Austin, C.P. (2003) DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation.  Hum. Mol. Genet., 12:1591-1608.

View Publications by Jill Morris listed in the National Library of Medicine (PubMed).