Timing of Sonic hedgehog and Gli1 expression segregates midbrain dopamine neurons.
Timing of Sonic hedgehog and Gli1 expression segregates midbrain dopamine neurons.
复制标题
DOI：
10.1002/cne.22711
复制
发表时间：
2011-10-15
影响因子：
2.5
通讯作者：
Ahn, Sohyun
中科院分区：
文献类型：
--
作者：
Hayes, Lindsay;Zhang, Zhiwei;Albert, Paul;Zervas, Mark;Ahn, Sohyun
关键词：
腹侧中脑（vMb）被组织成不同的解剖结构域，并包含功能不同的中脑多巴胺（mDA）神经元亚型的队列。我们测试的假设，遗传史和时间内的mDA神经元祖细胞的基因表达赋予空间多样性。使用遗传诱导的命运映射来标记不同胚胎阶段的Sonic hedgehog（Shh）和Gli 1谱系，我们对这两个谱系对mDA神经元结构域的贡献进行了定量和定性比较。动态变化Shh和Gli 1表达的vMb原基描绘了他们的空间贡献的E12.5 vMb：两个谱系首先有助于内侧域，但随后Gli 1谱系专门贡献的外侧vMb，而Shh谱系扩展更广泛的整个vMb。这两个谱系的分化的mDA神经元域的贡献最初偏向前方，并在整个发展的前/后VMB变得更加均匀。我们的研究结果表明，早期的Shh和Gli 1谱系指定的mDA神经元的黑质pars腹侧被盖区，而后期的Shh和Gli 1谱系保持其祖细胞状态更长的时间在后vMb延长生产的mDA神经元。总之，我们的研究表明，基因表达的时间沿着与神经祖细胞内的遗传谱系（Shh或Gli 1）分离mDA神经元到不同的空间域。
The ventral midbrain (vMb) is organized into distinct anatomical domains and contains cohorts of functionally distinct subtypes of midbrain dopamine (mDA) neurons. We tested the hypothesis that genetic history and timing of gene expression within mDA neuron progenitors impart spatial diversity. Using Genetic Inducible Fate Mapping to mark the Sonic hedgehog (Shh) and Gli1 lineages at varying embryonic stages, we performed a quantitative and qualitative comparison of the two lineages’ contribution to the mDA neuron domains. Dynamic changes in Shh and Gli1 expression in the vMb primordia delineated their spatial contribution to the E12.5 vMb: Both lineages first contributed to the medial domain, but subsequently the Gli1 lineage exclusively contributed to the lateral vMb while the Shh lineage expanded more broadly across the vMb. The contribution of both lineages to the differentiated mDA neuron domain was initially biased anteriorly and became more uniform across the anterior/posterior vMb throughout development. Our findings demonstrate that the early Shh and Gli1 lineages specify mDA neurons of the substantia nigra pars compacta while the late Shh and Gli1 lineages maintain their progenitor state longer in the posterior vMb to extend the production of mDA neurons in the ventral tegmental area. Together, our study demonstrates that the timing of gene expression along with the genetic lineage (Shh or Gli1) within the neural progenitors segregate mDA neurons into distinct spatial domains.
登录
查看更多内容
影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
影响因子：
16.2
作者：
Lammel, Stephan;Hetzel, Andrea;Roeper, Jochen
通讯作者：
Roeper, Jochen
影响因子：
16.2
作者：
HYNES, M;PORTER, JA;ROSENTHAL, A
通讯作者：
ROSENTHAL, A
影响因子：
9.8
作者：
通讯作者：
--
影响因子：
6.6
作者：
Laviolette, Steven R.
通讯作者：
Laviolette, Steven R.