Adult Neurogenesis: Reading for the Curious and a Breakthrough in Human Brain Imaging
As Jane Austen might have said: “It is a truth universally acknowledged, that a biological process in possession of a good molecular definition, must be in want of a disease.” In this case, the process in question is adult neurogenesis: the generation of new neurons at the inner face of the dentate gyrus of the hippocampus. A recent Science paper forms the core of this commentary as the work described within has the potential to transform our understanding of the field in two ways (Manganas et al., 2007). Firstly, it offers the first real chance of making definitive links to disease by permitting study of the phenomenon in human subjects, both well and unwell. This will strengthen the currently inferred links to psychiatric and other conditions. Secondly, the paper highlights a previously unexplored class of molecules that appear to be biomarkers for, and perhaps critical participants in the function of, the neuronal precursor cells...  Read more

View all comments by Ben Pickard

Several recent studies on disruptions of the DISC1 gene in mice illustrate the great potential of genetic approaches to studying functions of putative schizophrenia susceptibility genes but also signal the complexity of the problem. An initial rationale for studying the effects of mutations in DISC1 came from the discovery of the chromosomal translocation, resulting in a breakpoint in the DISC1 gene that co-segregated with major mental illness in a Scottish family (reviewed by Porteous et al., 2006). These clinical findings were followed by a number of association studies, which reported that numerous SNPs across the gene were associated with schizophrenia and mood disorders and a variety of intermediate phenotypes, suggesting that other problems in the DISC1 gene may exist in other subjects/populations.

Recent animal models designed to mimic partial loss of DISC1 function suggested that DISC1 is necessary to support development of the cerebral cortex as its loss resulted in impaired neurite...  Read more

View all comments by Barbara K. Lipska

I am very glad that our colleagues at Johns Hopkins University have published a very intriguing paper in Cell, showing a novel role for DISC1 in adult hippocampus. This is very consistent with previous publications (Miyoshi et al., 2003; Kamiya et al., 2005; and others; reviewed by Ishizuka et al., 2006), and adds a new insight into a key role for DISC1 during neurodevelopment. In short, DISC1 is a very important regulator in various phases of neurodevelopment, which is reinforced in this study. Specifically, DISC1 is crucial for regulating neuronal migration and dendritic development—for acceleration in the developing cerebral cortex, and for braking in the adult hippocampus.

There is precedence for signaling molecules playing the same role in different contexts, with the resulting molecular activity going in different directions. For example, FOXO3 (a member of the Forkhead transcription factor family) plays a role in...  Read more

View all comments by Akira Sawa

Recent findings, including the interactome study by Camargo et al., 2007, and this beautiful study by Duan and colleagues, implicate DISC1 (a leading candidate schizophrenia susceptibility gene) in synaptic function, consistent with prevailing ideas of the disorder as one of the synapse and connectivity (see Stephan et al., 2006). As we learn more about DISC1 and its protein partners, evidence demonstrating the importance of microtubules in the regulation of several neuronal processes (see Eastwood et al., 2006, for review) suggests that DISC1’s interactions with microtubule associated proteins (MAPs) may underpin its pathogenic influence.

DISC1 has been shown to bind to several MAPs (e.g., MAP1A, MIPT3) and other proteins important in regulating microtubule function (see Kamiya et al., 2005; Porteous et al., 2006). As a key component of the cell...  Read more

View all comments by Sharon Eastwood