Lhx1 and Lhx5 maintain the inhibitory-neurotransmitter status of interneurons in the dorsal spinal cord
Lhx1 and Lhx5 maintain the inhibitory-neurotransmitter status of interneurons in the dorsal spinal cord
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DOI：
10.1242/dev.02717
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发表时间：
2007-01-15
期刊：
影响因子：
4.6
通讯作者：
Goulding, Martyn
中科院分区：
文献类型：
--
作者：
Pillai, Andrea;Mansouri, Ahmed;Goulding, Martyn
Lhx 1和Lhx 5在发育中的脊髓中的多种中间神经元细胞类型中共表达。这些包括早期出生的dI 4和dl 6抑制性中间神经元，以及晚期出生的抑制性dIL（A）神经元（dIL（A）），所有这些都表达配对结构域转录因子Pax 2。虽然它似乎Lhx 1和Lhx 5不控制它们表达的神经元细胞类型的初始规格，我们已经发现了一个细胞自主的要求，无论是Lhx 1或Lhx 5，以维持在以后的发展阶段的背抑制性神经元的Pax 2，Pax 5和Pax 8的表达。Lhx1; Lhx 5双敲除小鼠表现出Gad 1和Viaat（Slc 32a 1）从E13.5开始下调，这与Pax 2表达的减少密切相关。Pax 2是背侧GABA能特性的关键因素，在背角中Pax 5和Pax 8的表达差异依赖于Pax 2。总之，我们的研究结果支持一种模型，其中背索中GABA能中间神经元的分化依赖于Pax 2，Lhx 1和Lhx 5有助于激活和维持Pax 2在这些细胞中的表达。因此，Lhx 1和Lhx 5与Pax 2、Pax 5和Pax 8共同发挥作用，在背角中间神经元中建立GABA能神经递质程序。
Lhx1 and Lhx5 are co-expressed in multiple interneuron cell types in the developing spinal cord. These include early-born dI4 and dl6 inhibitory interneurons, as well as late-born inhibitory dIL(A) neurons (dIL(A)), all of which express the paired-domain transcription factor Pax2. Although it appears that Lhx1 and Lhx5 do not control the initial specification of the neuronal cell types in which they are expressed, we have found a cell-autonomous requirement for either Lhx1 or Lhx5 to maintain the expression of Pax2, Pax5 and Pax8 in dorsal inhibitory neurons at later developmental stages. Lhx1; Lhx5 double-knockout mice exhibit a downregulation of Gad1 and Viaat (Slc32a1) from E13.5 onwards that is closely associated with a decrease in Pax2 expression. Pax2 is a key factor for dorsal GABAergic identity, with the expression of Pax5 and Pax8 being differentially dependent on Pax2 in the dorsal horn. In summary, our findings support a model in which the differentiation of GABAergic interneurons in the dorsal cord depends on Pax2, with Lhx1 and Lhx5 helping to activate and maintain Pax2 expression in these cells. Lhx1 and Lhx5 therefore function together with Pax2, Pax5 and Pax8 to establish a GABAergic inhibitory-neurotransmitter program in dorsal horn interneurons.