Department of Anatomy and Neurobiology, Wakayama Medical University, Wakayama, Japan.
Dev Neurosci. 2009;31(6):511-22. doi: 10.1159/000243715. Epub 2009 Sep 30.
A member of winged-helix/forkhead transcription factors, Foxp1, is expressed in the developing spinal cord during mouse embryogenesis. To shed light on the potential role of Foxp1 in neurons of the developing spinal cord, we investigated the detailed expression pattern of Foxp1 between embryonic day (E) 9.5 and E17.5. At E10.25, some postmitotic neurons with strong expression of Foxp1 (Foxp1(high)) were first detected in the ventral half of the brachial spinal cord. By E11.5, Foxp1(high) neurons increased in the ventral spinal cord at the limb levels. All of Foxp1(high) neurons at the limb levels were Islet2(+)/Lhx3(-) motor neurons (MNs) of the lateral motor column and some neurons that expressed Foxp1 weakly (Foxp1(low)) at the thoracic level were MNs of the preganglionic motor column. Between E12.5 and E17.5, Foxp1(low) neurons were also observed in the intermediate zone throughout the ventral spinal cord, all of which were Pax2(+), En1(+), Evx1(-), Chx10(-), Gata3(-), and Lhx3(-) V1 interneurons. Interestingly, no colocalization of Foxp1 with Lhx3 was observed in the developing spinal cord. In addition, overexpression of Foxp1 markedly attenuated the endogenous expression of Lhx3 in a neuroendocrine cell line. Chromatin immunoprecipitation assays in a neuronal cell line and E13.5 spinal cords revealed an interaction between Foxp1 and the consensus motif in the Lhx3 promoter. These results suggest that Foxp1 may play some important roles in the determination of neuronal fates of the ventral spinal cord, possibly through the suppression of Lhx3 expression.
翼状螺旋/叉头转录因子家族的一个成员 Foxp1 在小鼠胚胎发生过程中表达于发育中的脊髓。为了阐明 Foxp1 在发育中的脊髓神经元中的潜在作用,我们研究了 Foxp1 在胚胎期 9.5 天(E)至 17.5 天(E)之间的详细表达模式。在 E10.25 时,首先在臂部脊髓的腹侧半部分检测到一些具有强 Foxp1 表达的有丝分裂后神经元(Foxp1(high))。到 E11.5 时,Foxp1(high)神经元在肢体水平的脊髓腹侧增加。所有肢体水平的 Foxp1(high)神经元都是外侧运动柱的 Islet2(+)/Lhx3(-)运动神经元(MNs),而在胸段表达较弱 Foxp1 的一些神经元(Foxp1(low))是节前运动柱的 MNs。在 E12.5 至 E17.5 期间,Foxp1(low)神经元也在整个脊髓腹侧的中间区中被观察到,它们均为 Pax2(+)、En1(+)、Evx1(-)、Chx10(-)、Gata3(-)和 Lhx3(-) V1 中间神经元。有趣的是,在发育中的脊髓中未观察到 Foxp1 与 Lhx3 的共定位。此外,Foxp1 的过表达显著减弱了神经内分泌细胞系中内源性 Lhx3 的表达。在神经元细胞系和 E13.5 脊髓中的染色质免疫沉淀测定揭示了 Foxp1 与 Lhx3 启动子中的共识基序之间的相互作用。这些结果表明,Foxp1 可能在脊髓腹侧神经元命运的决定中发挥一些重要作用,可能是通过抑制 Lhx3 的表达。