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TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons.


ABSTRACT: In the peripheral nervous system, target tissues control the final size of innervating neuronal populations by producing limited amounts of survival-promoting neurotrophic factors during development. However, it remains largely unknown if the same principle works to regulate the size of neuronal populations in the developing brain. Here we show that neurotrophin signaling mediated by the TrkB receptor controls striatal size by promoting the survival of developing medium-sized spiny neurons (MSNs). Selective deletion of the gene for the TrkB receptor in striatal progenitors, using the Dlx5/6-Cre transgene, led to a hindpaw-clasping phenotype and a 50% loss of MSNs without affecting striatal interneurons. This loss resulted mainly from increased apoptosis of newborn MSNs within their birthplace, the lateral ganglionic eminence. Among MSNs, those expressing the dopamine receptor D2 (DRD2) were most affected, as indicated by a drastic loss of these neurons and specific down-regulation of the DRD2 and enkephalin. This specific phenotype of mutant animals is likely due to preferential TrkB expression in DRD2 MSNs. These findings suggest that neurotrophins can control the size of neuronal populations in the brain by promoting the survival of newborn neurons before they migrate to their final destinations.

SUBMITTER: Baydyuk M 

PROVIDER: S-EPMC3029684 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons.

Baydyuk Maryna M   Russell Theron T   Liao Guey-Ying GY   Zang Keling K   An Juan Ji JJ   Reichardt Louis French LF   Xu Baoji B  

Proceedings of the National Academy of Sciences of the United States of America 20110104 4


In the peripheral nervous system, target tissues control the final size of innervating neuronal populations by producing limited amounts of survival-promoting neurotrophic factors during development. However, it remains largely unknown if the same principle works to regulate the size of neuronal populations in the developing brain. Here we show that neurotrophin signaling mediated by the TrkB receptor controls striatal size by promoting the survival of developing medium-sized spiny neurons (MSNs  ...[more]

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