Genethliou Nicholas, Panayiotou Elena, Panayi Helen, Orford Michael, Mean Richard, Lapathitis George, Malas Stavros
The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios 2370, Nicosia, Cyprus.
Biochem Biophys Res Commun. 2009 Apr 24;382(1):69-73. doi: 10.1016/j.bbrc.2009.02.134. Epub 2009 Mar 1.
During ventral spinal cord (vSC) development, the p3 and pMN progenitor domain boundary is thought to be maintained by cross-repressive interactions between NKX2.2 and PAX6. Using loss-of-function analysis during the neuron-glial fate switch we show that the identity of the p3 domain is not maintained by the repressive function of NKX2.2 on Pax6 expression, even in the absence of NKX2.9. We further show that NKX2.2 is necessary to induce the expression of Slit1 and Sulfatase 1 (Sulf1) in the vSC in a PAX6-independent manner. Conversely, we show that PAX6 regulates Sulf1/Slit1 expression in the vSC in an NKX2.2/NKX6.1-independent manner. Consequently, deregulation of Sulf1 expression in Pax6-mutant embryos has stage-specific implications on neural patterning, associated with enhancement of Sonic Hedgehog activity. On the other hand, deregulation of Slit1 expression in gliogenic neural progenitors leads to changes in Astrocyte subtype identity. These data provide important insights into specific functions of PAX6 and NKX2.2 during glial cell specification that have so far remained largely unexplored.
在脊髓腹侧（vSC）发育过程中，p3和pMN祖细胞结构域边界被认为是由NKX2.2和PAX6之间的相互抑制作用维持的。在神经元-胶质细胞命运转换过程中使用功能丧失分析，我们发现即使在没有NKX2.9的情况下，p3结构域的身份也不是由NKX2.2对Pax6表达的抑制功能维持的。我们进一步表明，NKX2.2以不依赖PAX6的方式诱导vSC中Slit1和硫酸酯酶1（Sulf1）的表达是必要的。相反，我们表明PAX6以不依赖NKX2.2/NKX6.1的方式调节vSC中Sulf1/Slit1的表达。因此，Pax6突变胚胎中Sulf1表达的失调对神经模式形成具有阶段特异性影响，与音猬因子（Sonic Hedgehog）活性增强有关。另一方面，胶质生成神经祖细胞中Slit1表达的失调导致星形胶质细胞亚型身份的变化。这些数据为PAX6和NKX2.2在胶质细胞特化过程中的特定功能提供了重要见解，而这些功能迄今为止在很大程度上仍未被探索。
