Institute of Molecular and Cellular Anatomy, Ulm University, 89081 Ulm, Germany.
Development. 2012 May;139(10):1831-41. doi: 10.1242/dev.072850. Epub 2012 Apr 4.
Dorsal spinal cord neurons receive and integrate somatosensory information provided by neurons located in dorsal root ganglia. Here we demonstrate that dorsal spinal neurons require the Krüppel-C(2)H(2) zinc-finger transcription factor Bcl11a for terminal differentiation and morphogenesis. The disrupted differentiation of dorsal spinal neurons observed in Bcl11a mutant mice interferes with their correct innervation by cutaneous sensory neurons. To understand the mechanism underlying the innervation deficit, we characterized changes in gene expression in the dorsal horn of Bcl11a mutants and identified dysregulated expression of the gene encoding secreted frizzled-related protein 3 (sFRP3, or Frzb). Frzb mutant mice show a deficit in the innervation of the spinal cord, suggesting that the dysregulated expression of Frzb can account in part for the phenotype of Bcl11a mutants. Thus, our genetic analysis of Bcl11a reveals essential functions of this transcription factor in neuronal morphogenesis and sensory wiring of the dorsal spinal cord and identifies Frzb, a component of the Wnt pathway, as a downstream acting molecule involved in this process.
背根神经节中的神经元向背柱脊髓神经元提供感觉信息，后者接收并整合这些信息。我们发现，Krüppel-C(2)H(2)锌指转录因子 Bcl11a 对于背柱脊髓神经元的终末分化和形态发生是必需的。Bcl11a 突变小鼠的背柱脊髓神经元分化异常，这干扰了其与皮肤感觉神经元的正确神经支配。为了了解神经支配缺陷的机制，我们对 Bcl11a 突变体的背角中的基因表达变化进行了表征，并鉴定出编码分泌型卷曲相关蛋白 3（sFRP3，或 Frzb）的基因表达失调。Frzb 突变小鼠的脊髓神经支配缺陷，表明 Frzb 的表达失调部分可以解释 Bcl11a 突变体的表型。因此，我们对 Bcl11a 的遗传分析揭示了该转录因子在背柱脊髓神经元形态发生和感觉神经布线中的重要功能，并鉴定出 Frzb（Wnt 通路的一个组成部分）作为参与该过程的下游作用分子。
