PMC:2944667 / 1373-4587 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2944667","sourcedb":"PMC","sourceid":"2944667","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2944667","text":"Introduction\nThere is a growing appreciation for the neurodevelopmental underpinnings of many psychiatric disorders. While the importance of the growth and structuring of the brain has long been recognized for disorders that begin in childhood such as autism, language disorders or mental retardation, there is consensus building that adult-onset mental disorders also have origins early in neurodevelopment. In order to expand our understanding of these origins, the National Institute of Mental Health (NIMH) is investing in studies of developmental neurobiology, choosing one of its strategies to be the support of “research to improve our basic understanding of the development, structure, and function of neural circuits, with a focus on those most relevant to mental disorders” (NAMHC, 2008). Forwarding this agenda requires a better understanding of the neurobiology of neural stem cells (NSCs) and the factors that regulate them in the developing brain.\nNeural stem cells can be defined as self-renewing, multipotent cells that are present in both the embryonic and adult brain. Several recent research findings demonstrate that psychiatric illness may begin with abnormal specification, growth, expansion and differentiation of embryonic NSCs. For example, candidate susceptibility genes for schizophrenia, autism and major depression include those specifying the signaling molecule Disrupted In Schizophrenia-1 (DISC-1), the homeodomain gene engrailed-2 (EN-2), and several receptor tyrosine kinases (RTKs), including brain-derived neurotrophic factor (BDNF) and fibroblast growth factors (FGF), all of which have been shown to play important roles in NSCs or neuronal precursors. Hypotheses about how some of these factors relate to psychiatric disorders are now the focus of much neurodevelopmental work (see several reviews: Arnold et al., 2005; Buckley et al., 2007; Eisch et al., 2008; Thomas and Peterson, 2008; Jaaro-Peled et al., 2009; Vaccarino et al., 2009).\nThis review will lay out some aspects of the new frontier represented by stem cells for understanding the origins of mental illness. In section I, we will review embryonic central nervous system (CNS) development, focusing on forebrain NSCs and the role of the RTKs, such as FGF receptors (FGFRs), in the earliest developmental processes. RTKs are transmembrane proteins that, upon binding a ligand presented or secreted by nearby cells, phosphorylate intracellular signaling molecules and transduce cell-to-cell signaling in the brain. FGF receptors (FGFRs) are among the earliest RTKs expressed in the developing brain, but also continue to be expressed in the mature brain.\nFollowing this review of NSCs and FGFs in embryonic development, in section II we will describe neurobiological findings in clinical populations that support disrupted embryonic stem cell activity. In section III, adult NSC functioning and connections with mental illness will be reviewed. In section IV, we will discuss how new research with inducible pluripotent stem cells derived from patients with neuropsychiatric disorders may further our understanding of developmental aspect of psychopathology and reveal potential targets for psychiatric treatment.","divisions":[{"label":"title","span":{"begin":0,"end":12}},{"label":"p","span":{"begin":13,"end":961}},{"label":"p","span":{"begin":962,"end":1978}},{"label":"p","span":{"begin":1979,"end":2655}}],"tracks":[{"project":"TEST0","denotations":[{"id":"20877431-162-170-637112","span":{"begin":1853,"end":1857},"obj":"[\"15581715\"]"},{"id":"20877431-184-192-637113","span":{"begin":1875,"end":1879},"obj":"[\"17524622\"]"},{"id":"20877431-204-212-637114","span":{"begin":1895,"end":1899},"obj":"[\"19005040\"]"},{"id":"20877431-231-239-637115","span":{"begin":1922,"end":1926},"obj":"[\"18590054\"]"},{"id":"20877431-231-239-637116","span":{"begin":1948,"end":1952},"obj":"[\"19712980\"]"},{"id":"20877431-231-239-637117","span":{"begin":1972,"end":1976},"obj":"[\"18850329\"]"}],"attributes":[{"subj":"20877431-162-170-637112","pred":"source","obj":"TEST0"},{"subj":"20877431-184-192-637113","pred":"source","obj":"TEST0"},{"subj":"20877431-204-212-637114","pred":"source","obj":"TEST0"},{"subj":"20877431-231-239-637115","pred":"source","obj":"TEST0"},{"subj":"20877431-231-239-637116","pred":"source","obj":"TEST0"},{"subj":"20877431-231-239-637117","pred":"source","obj":"TEST0"}]},{"project":"0_colil","denotations":[{"id":"20877431-15581715-637112","span":{"begin":1853,"end":1857},"obj":"15581715"},{"id":"20877431-17524622-637113","span":{"begin":1875,"end":1879},"obj":"17524622"},{"id":"20877431-19005040-637114","span":{"begin":1895,"end":1899},"obj":"19005040"},{"id":"20877431-18590054-637115","span":{"begin":1922,"end":1926},"obj":"18590054"},{"id":"20877431-19712980-637116","span":{"begin":1948,"end":1952},"obj":"19712980"},{"id":"20877431-18850329-637117","span":{"begin":1972,"end":1976},"obj":"18850329"}],"attributes":[{"subj":"20877431-15581715-637112","pred":"source","obj":"0_colil"},{"subj":"20877431-17524622-637113","pred":"source","obj":"0_colil"},{"subj":"20877431-19005040-637114","pred":"source","obj":"0_colil"},{"subj":"20877431-18590054-637115","pred":"source","obj":"0_colil"},{"subj":"20877431-19712980-637116","pred":"source","obj":"0_colil"},{"subj":"20877431-18850329-637117","pred":"source","obj":"0_colil"}]},{"project":"2_test","denotations":[{"id":"20877431-15581715-38520389","span":{"begin":1853,"end":1857},"obj":"15581715"},{"id":"20877431-17524622-38520390","span":{"begin":1875,"end":1879},"obj":"17524622"},{"id":"20877431-19005040-38520391","span":{"begin":1895,"end":1899},"obj":"19005040"},{"id":"20877431-18590054-38520392","span":{"begin":1922,"end":1926},"obj":"18590054"},{"id":"20877431-19712980-38520393","span":{"begin":1948,"end":1952},"obj":"19712980"},{"id":"20877431-18850329-38520394","span":{"begin":1972,"end":1976},"obj":"18850329"}],"attributes":[{"subj":"20877431-15581715-38520389","pred":"source","obj":"2_test"},{"subj":"20877431-17524622-38520390","pred":"source","obj":"2_test"},{"subj":"20877431-19005040-38520391","pred":"source","obj":"2_test"},{"subj":"20877431-18590054-38520392","pred":"source","obj":"2_test"},{"subj":"20877431-19712980-38520393","pred":"source","obj":"2_test"},{"subj":"20877431-18850329-38520394","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#93aaec","default":true},{"id":"0_colil","color":"#c4ec93"},{"id":"2_test","color":"#ec93de"}]}]}}