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Title

Thyroid hormone triggers the developmental loss of axonal regenerative capacity via thyroid hormone receptor α1 and krüppel-like factor 9 in Purkinje cells

AuthorsAvci, Hasan X.; Lebrun, Clement; Wehrlé, Rosine; Doulazmi, Mohamed; Chatonnet, Fabrice; Morel, Marie-Pierre; Ema, Masatsugu; Vodjdani, Guilan; Sotelo, Constantino; Flamant, Frédéric; Dusart, Isabelle
Issue Date2012
PublisherNational Academy of Sciences (U.S.)
CitationProceedings of the National Academy of Sciences of the United States of America 109(35): 14206-14211 (2012)
AbstractNeurons in the CNS of higher vertebrates lose their ability to regenerate their axons at a stage of development that coincides with peak circulating thyroid hormone (T3) levels. Here, we examined whether this peak in T3 is involved in the loss of axonal regenerative capacity in Purkinje cells (PCs). This event occurs at the end of the first postnatal week in mice. Using organotypic culture, we found that the loss of axon regenerative capacity was triggered prematurely by early exposure of mouse PCs to T3, whereas it was delayed in the absence of T3. Analysis of mutant mice showed that this effect was mainly mediated by the T3 receptor α1. Using gain- and loss-of-function approaches, we also showed that Krüppel-like factor 9 was a key mediator of this effect of T3.These results indicate that the sudden physiological increase in T3 during development is involved in the onset of the loss of axon regenerative capacity in PCs. This loss of regenerative capacity might be part of the general program triggered by T3 throughout the body, which adapts the animal to its postnatal environment.
URIhttp://hdl.handle.net/10261/71586
DOI10.1073/pnas.1119853109
Identifiersdoi: 10.1073/pnas.1119853109
issn: 0027-8424
e-issn: 1091-6490
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