| Intrinsically determined cell death of developing cortical interneurons. | |
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MedLine Citation:
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PMID: 23041929 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Cortical inhibitory circuits are formed by γ-aminobutyric acid (GABA)-secreting interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis, is that cortical interneurons are overproduced, and then after their migration into cortex the excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we characterize the developmental cell death of mouse cortical interneurons in vivo, in vitro and after transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax (Bcl-2-associated X)-dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by neurons of the central nervous system. Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Taken together, our findings indicate that interneuron cell death is determined intrinsically, either cell-autonomously or through a population-autonomous competition for survival signals derived from other interneurons. |
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Authors:
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Derek G Southwell; Mercedes F Paredes; Rui P Galvao; Daniel L Jones; Robert C Froemke; Joy Y Sebe; Clara Alfaro-Cervello; Yunshuo Tang; Jose M Garcia-Verdugo; John L Rubenstein; Scott C Baraban; Arturo Alvarez-Buylla |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-07 |
Journal Detail:
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Title: Nature Volume: - ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Neuroscience Graduate Program, University of California, San Francisco, California 94143, USA [2] Departments of Neuroscience and Neurosurgery, and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research; University of California, San Francisco, California 94143, USA [3] Medical Scientist Training Program, University of California, San Francisco, California 94143, USA [4]. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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