Telethon Institute of Genetics and Medicine, Developmental Disorders Program, 80131 Naples, Italy.
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3576-81. doi: 10.1073/pnas.0911792107. Epub 2010 Feb 2.
Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise.
在皮质祖细胞中具有表达梯度的转录因子通过控制不同神经元亚型的区域特异性分化，产生不同的运动和感觉皮层区域。然而，这种区域限制控制的分子机制尚不清楚。在这里，我们表明，COUP-TFI 通过抑制皮质脊髓运动神经元（CSMN）分化程序来控制感觉皮层中 CSMN 的出生和特化的时间。COUP-TFI 功能的丧失导致具有 CSMN 主要特征的神经元在区域特异性上过早产生，这些神经元投射到包括脊髓在内的亚脑结构。同时，真正的 CSMN 分化不精确，不会投射到脑桥以外，导致皮质 COUP-TFI 功能丧失的成年小鼠的精细运动功能受损。我们的研究结果表明，COUP-TFI 在皮质发生过程中对 CSMN 的精确分化发挥了关键的区域和时间控制作用，从而使运动和感觉区域的特定功能特征得以产生。
