Thyroid hormone triggers the developmental loss of axonal regenerative capacity via thyroid hormone receptor α1 and krüppel-like factor 9 in Purkinje cells.
Neurons 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 (T(3)) levels. Here, we examined whether this peak in T(3) 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 T(3), whereas it was delayed in the absence of T(3). Analysis of mutant mice showed that this effect was mainly mediated by the T(3) 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 T(3). These results indicate that the sudden physiological increase in T(3) 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 T(3) throughout the body, which adapts the animal to its postnatal environment.
Université Pierre et Marie Curie (UPMC) Paris 06, Unité Mixte de Recherche 7102, 75005 Paris,  France.
Hasan X
HX
Avci
Clement
C
Lebrun
Rosine
R
Wehrlé
Mohamed
M
Doulazmi
Fabrice
F
Chatonnet
Marie-Pierre
MP
Morel
Masatsugu
M
Ema
Guilan
G
Vodjdani
Constantino
C
Sotelo
Frédéric
F
Flamant
Isabelle
I
Dusart
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D019771:Axotomy; D002531:Cerebellum / Q000254:growth & development / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
C489675:Klf9 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine