Merchan-Sala Paloma, Nardini Diana, Waclaw Ronald R, Campbell Kenneth
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
J Comp Neurol. 2017 Sep 1;525(13):2805-2819. doi: 10.1002/cne.24232. Epub 2017 May 22.
The striatum is the major component of the basal ganglia and is well known to play a key role in the control of motor function via balanced output from the indirect (iSPNs) and direct pathway striatal projection neurons (dSPNs). Little is known, however, about the molecular genetic mechanisms that control the formation of the iSPNs versus dSPNs. We show here that the SoxE family member, Sox8, is co-expressed with the dSPN markers, Isl1 and Ebf1, in the developing striatum. Moreover, dSPNs, as marked by Isl1-cre fate map, express Sox8 in the embryonic striatum and Sox8-EGFP BAC transgenic mice specifically reveal the direct pathway axons during development. These EGFP axons are first observed to reach their midbrain target, the substantia nigra pars reticulata (SNr), at E14 in the mouse with a robust connection observed already at birth. The selective expression of EGFP in dSPNs of Sox8-EGFP BAC mice is maintained at postnatal timepoints. Sox8 is known to be expressed in oligodendrocyte precursor cells (OPCs) together with other SoxE factors and we show here that the EGFP signal co-localizes with the OPC markers throughout the brain. Finally, we show that Sox8-EGFP BAC mice can be used to interrogate the altered dSPN development in Isl1 conditional mutants including aberrant axonal projections detected already at embryonic timepoints. Thus, Sox8 represents an early and specific marker of embryonic dSPNs and the Sox8-EGFP BAC transgenic mice are an excellent tool to study the development of basal ganglia circuitry.
纹状体是基底神经节的主要组成部分，众所周知，它通过间接通路纹状体投射神经元（iSPNs）和直接通路纹状体投射神经元（dSPNs）的平衡输出在运动功能控制中发挥关键作用。然而，关于控制iSPNs与dSPNs形成的分子遗传机制却知之甚少。我们在此表明，SoxE家族成员Sox8在发育中的纹状体中与dSPN标记物Isl1和Ebf1共同表达。此外，以Isl1-cre命运图谱标记的dSPNs在胚胎纹状体中表达Sox8，并且Sox8-EGFP BAC转基因小鼠在发育过程中特异性地揭示了直接通路轴突。在小鼠胚胎第14天首次观察到这些EGFP轴突到达它们的中脑靶点黑质网状部（SNr），出生时已观察到牢固的连接。Sox8-EGFP BAC小鼠dSPNs中EGFP的选择性表达在出生后各时间点得以维持。已知Sox8与其他SoxE因子一起在少突胶质前体细胞（OPCs）中表达，我们在此表明，EGFP信号在全脑与OPC标记物共定位。最后，我们表明Sox8-EGFP BAC小鼠可用于研究Isl1条件性突变体中dSPN发育的改变，包括在胚胎时间点就检测到的异常轴突投射。因此，Sox8是胚胎dSPNs的早期特异性标记物，Sox8-EGFP BAC转基因小鼠是研究基底神经节回路发育的优秀工具。
