Peripheral somatosensory input is modulated in the dorsal spinal cord by a network of excitatory and inhibitory interneurons. PTF1A is a transcription factor essential in dorsal neural tube progenitors for specification of these inhibitory neurons. Thus, mechanisms regulating Ptf1a expression are key for generating neuronal circuits underlying somatosensory behaviors. Mutations targeted to distinct cis-regulatory elements for Ptf1a in mice, tested the in vivo contribution of each element individually and in combination. Mutations in an autoregulatory enhancer resulted in reduced levels of PTF1A, and reduced numbers of specific dorsal spinal cord inhibitory neurons, particularly those expressing Pdyn and Gal Although these mutants survive postnatally, at ∼3-5 wk they elicit a severe scratching phenotype. Behaviorally, the mutants have increased sensitivity to itch, but acute sensitivity to other sensory stimuli such as mechanical or thermal pain is unaffected. We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits.

中文翻译：

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对Ptf1a转录的正向自动反馈调节产生了产生痒电路神经元所需的PTF1A水平。

周围体感输入通过兴奋性和抑制性中间神经元网络在脊髓背侧进行调节。PTF1A是背神经管祖细胞中必需的转录因子，用于规范这些抑制性神经元。因此，调节Ptf1a表达的机制是产生体感行为基础的神经元回路的关键。靶向小鼠Ptf1a独特的顺式调控元件的突变，分别测试了每种元素在体内的作用，并结合在一起进行了测试。自调节增强子的突变导致PTF1A水平降低，特异性背脊髓抑制神经元数量减少，特别是表达Pdyn和Gal的神经元数量减少。尽管这些突变体在出生后存活，但在约3-5周时会引起严重的挠性表型。行为上 突变体对瘙痒的敏感性增加，但对其他感觉刺激（如机械或热痛）的急性敏感性不受影响。我们证明了积极的转录自调节反馈的要求，以达到生成正确平衡的神经元回路所必需的神经元特定因子PTF1A的水平。