Miesegaes George R, Klisch Tiemo J, Thaller Christina, Ahmad Kaashif A, Atkinson Richard C, Zoghbi Huda Y
Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Dev Biol. 2009 Mar 15;327(2):339-51. doi: 10.1016/j.ydbio.2008.12.016. Epub 2008 Dec 25.
At spinal levels, sensory information pertaining to body positioning (proprioception) is relayed to the cerebellum by the spinocerebellar tracts (SCTs). In the past we revealed the basic helix-loop-helix transcription factor Atoh1 (Math1) to be important for establishing Dorsal Progenitor 1 (DP1) commissural interneurons, which comprise a subset of proprioceptive interneurons. Given there exists multiple subdivisions of the SCT we asked whether Atoh1 may also play a role in specifying other cell types in the spinal cord. Here, we reveal the generation of at least three DP1 derived interneuron populations that reside at spatially restricted positions along the rostral-caudal axis. Each of these cell populations expresses distinct markers and anatomically coincides with the cell bodies of the various subdivisions of the SCT. In addition, we found that as development proceeds (e.g. by E13.5) Atoh1 expression becomes apparent in the dorsal midline in the region of the roof plate (RP). Interestingly, we find that cells derived from Atoh1 expressing RP progenitors express SSEA-1, and in the absence of Atoh1 these progenitors become SOX9 positive. Altogether we reveal the existence of multiple Atoh1 dependent cell types in the spinal cord, and uncover a novel progenitor domain that arises late in development.
在脊髓水平,与身体位置相关的感觉信息(本体感觉)通过脊髓小脑束(SCTs)传递至小脑。过去我们发现碱性螺旋-环-螺旋转录因子Atoh1(Math1)对于建立背侧祖细胞1(DP1)连合中间神经元很重要,DP1连合中间神经元是本体感觉中间神经元的一个子集。鉴于SCT存在多个细分部分,我们询问Atoh1是否也可能在脊髓中其他细胞类型的特化中发挥作用。在这里,我们揭示了至少三种源自DP1的中间神经元群体的产生,它们沿头尾轴位于空间受限的位置。这些细胞群体中的每一个都表达不同的标志物,并且在解剖学上与SCT各个细分部分的细胞体相吻合。此外,我们发现随着发育的进行(例如在E13.5时),Atoh1在顶板(RP)区域的背侧中线中表达明显。有趣的是,我们发现源自表达Atoh1的RP祖细胞的细胞表达阶段特异性胚胎抗原-1(SSEA-1),并且在没有Atoh1的情况下,这些祖细胞变为SOX9阳性。我们总共揭示了脊髓中存在多种依赖Atoh1的细胞类型,并发现了一个在发育后期出现的新的祖细胞区域。