Immunohistochemical analysis of Disc1 expression in the developing and adult hippocampus Kate D. Meyer, Jill A. Morris * Human Molecular Genetics Program, Department of Pediatrics, Children’s Memorial Research Center, Feinberg School of Medicine, Northwestern University, 2300 Children’s Plaza, P.O. Box 211, Chicago, IL 60614, USA article info Article history: Received 12 February 2008 Received in revised form 13 June 2008 Accepted 16 June 2008 Available online 24 June 2008 Keywords: DISC1 Disrupted-In-Schizophrenia 1 Schizophrenia Susceptibility gene Hippocampus Immunohistochemistry Postnatal Development Granule cell Dentate gyrus Ammon’s horn CA1 CA3 Adult neurogenesis Migration Prox1 Calbindin Calretinin Ki67 GAD 67 abstract In recent years, Disrupted-In-Schizophrenia 1 (DISC1) has emerged as one of the most promising candidate genes whose disruption confers an increased risk for schizophrenia. Cell biology studies have implicated DISC1 in key neurodevelopmental processes including neurite outgrowth and neuronal migration. In situ hybridization analysis has revealed that Disc1 is expressed in the hypothalamus, olfactory bulbs, the developing cerebral cortex and the hippocampus. The hippocampus is of particular interest because abnormalities in hippocampal volume and function have been consistently reported in schizophrenics. Moreover, DISC1 mutations have been associated with abnormal activation of the hippocampus in humans. Given the involvement of the hippocampus in the pathophysiology of schizophrenia, there is an intriguing possibility that disruption of DISC1 may increase schizophrenia susceptibility by altering the normal development and function of the hippocampus. In order to contribute to our understanding of DISC1’s role in the hippocampus, we have performed a detailed analysis of the Disc1 expression pat- tern in the mouse hippocampus throughout development. We report that Disc1 is expressed throughout the hippocampus during embryonic development, with expression becoming increasingly specialized in Ammon’s horn and dentate gyrus granule cells within the first postnatal week. This expression pattern remains consistent into adulthood, with a noted decrease in Disc1 expression in the adult CA1. Disc1 is also expressed in proliferating cells in the adult subgranular zone, as well as in a subset of GABAergic interneurons. Our results are the first report of a detailed immunohistochemical analysis of the ontogeny of Disc1 expression within the hippocampus. Ó 2008 Elsevier B.V. All rights reserved. 1. Results and discussion Disrupted-In-Schizophrenia 1 (DISC1) is a schizophrenia suscepti- bility gene that was originally identified in a large Scottish family with a (1:11) (q42.1;q14.3) chromosomal translocation segregat- ing with schizophrenia (Millar et al., 2000). Since then, DISC1 has been associated with schizophrenia in multiple populations, including North American, Taiwanese, Japanese and Finnish (re- viewed in Chubb et al., 2008). In situ hybridization studies in the rodent brain have revealed that Disc1 is expressed in the develop- ing hippocampus and cerebral cortex (Austin et al., 2004). In the adult brain, Disc1 mRNA is expressed in the hippocampus, cerebel- lum, cerebral cortex and olfactory bulbs (Ma et al., 2002). A similar expression pattern is observed in the human brain, with notable DISC1 mRNA expression in areas implicated in schizophrenia, such as the dorsolateral prefrontal cortex and the hippocampus (Lipska et al., 2006). That Disc1 is highly expressed in the hippocampus both during development and into adulthood is especially intrigu- ing given the frequency with which hippocampal deficits are ob- served in schizophrenia. Indeed, abnormalities in both hippocampal function and structure are hallmarks of the schizo- phrenic brain; specifically, reduced hippocampal volume (Nelson et al., 1998), abnormal activity patterns (Niznikiewicz et al., 2003), and deficits in hippocampal-related tasks such as episodic memory (Reichenberg and Harvey, 2007) are consistently seen. Furthermore, studies in human subjects have shown that variation of DISC1 is associated with impaired hippocampal structure and function in both schizophrenic patients and healthy carriers (Callicott et al., 2005). These studies underscore the importance 1567-133X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.gep.2008.06.005 * Corresponding author. Tel.: +1 773 755 6351; fax: +1 773 755 6345. E-mail address: j-morris4@northwestern.edu (J.A. Morris). Gene Expression Patterns 8 (2008) 494–501 Contents lists available at ScienceDirect Gene Expression Patterns journal homepage: www.elsevier.com/locate/gep