Institute of Human Genetics, CNRS UPR1142, Montpellier, France.
Nat Neurosci. 2011 Jan;14(1):37-44. doi: 10.1038/nn.2700. Epub 2010 Dec 5.
Developmental axon pruning is a general mechanism that is required for maturation of neural circuits. During Drosophila metamorphosis, the larval-specific dendrites and axons of early γ neurons of the mushroom bodies are pruned and replaced by adult-specific processes. We found that the nuclear receptor ftz-f1 is required for this pruning, activates expression of the steroid hormone receptor EcR-B1, whose activity is essential for γ remodeling, and represses expression of Hr39, an ftz-f1 homologous gene. If inappropriately expressed in the γ neurons, HR39 inhibits normal pruning, probably by competing with endogenous FTZ-F1, which results in decreased EcR-B1 expression. EcR-B1 was previously identified as a target of the TGFβ signaling pathway. We found that the ftz-f1 and Hr39 pathway apparently acts independently of TGFβ signaling, suggesting that EcR-B1 is the target of two parallel molecular pathways that act during γ neuron remodeling.
发育中的轴突修剪是一种普遍的机制，对于神经回路的成熟是必需的。在果蝇变态过程中，蘑菇体中早期γ神经元的幼虫特异性树突和轴突被修剪，并被成年特异性过程所取代。我们发现，核受体 ftz-f1 是这种修剪所必需的，它激活了类固醇激素受体 EcR-B1 的表达，其活性对于 γ 重塑是必不可少的，并抑制了 ftz-f1 同源基因 Hr39 的表达。如果在 γ 神经元中不恰当地表达，HR39 会抑制正常的修剪，可能是通过与内源性 FTZ-F1 竞争，从而导致 EcR-B1 表达减少。EcR-B1 先前被鉴定为 TGFβ 信号通路的靶标。我们发现，ftz-f1 和 Hr39 途径显然独立于 TGFβ 信号，表明 EcR-B1 是在 γ 神经元重塑过程中两个平行的分子途径的靶标。
