Müller Myriam, Jabs Normund, Lorke Dietrich E, Fritzsch Bernd, Sander Maike
Center for Molecular Neurobiology, Martinistrasse 85, 20251 Hamburg, Germany.
Development. 2003 Dec;130(23):5815-26. doi: 10.1242/dev.00815. Epub 2003 Oct 8.
As many studies have focused on the mechanisms of motoneuron specification, little is known about the factors that control the subsequent development of postmitotic motoneurons. Previously, we showed that the transcription factor Nkx6.1 is required for the early specification of somatic motoneuron progenitors in the spinal cord. Our present analysis of hindbrain motoneuron development in Nkx6.1-deficient mouse embryos reveals that the early specification of branchio-motoneurons is independent of Nkx6.1 function, but that it is required for their subsequent development. In Nkx6.1 mutant mice, we observed defects in the migration, as well as in the axon projections of branchio-motoneurons. A detailed analysis of the migratory defect in facial branchio-motoneurons reveals ectopic expression of the cell surface receptors Ret and Unc5h3 in premigratory neurons, but no changes in the rhombomeric environment. Taken together, our findings demonstrate a requirement for Nkx6.1 in the development of postmitotic motoneurons, and suggest a cell-autonomous function in the control of branchio-motoneuron migration.
由于许多研究都集中在运动神经元特化的机制上，对于控制有丝分裂后运动神经元后续发育的因素知之甚少。此前，我们发现转录因子Nkx6.1是脊髓中体运动神经元祖细胞早期特化所必需的。我们目前对Nkx6.1基因缺失的小鼠胚胎后脑运动神经元发育的分析表明，鳃运动神经元的早期特化独立于Nkx6.1的功能，但在其后续发育中是必需的。在Nkx6.1突变小鼠中，我们观察到鳃运动神经元在迁移以及轴突投射方面存在缺陷。对面部鳃运动神经元迁移缺陷的详细分析显示，迁移前神经元中细胞表面受体Ret和Unc5h3异位表达，但菱脑节环境没有变化。综上所述，我们的研究结果表明有丝分裂后运动神经元的发育需要Nkx6.1，并提示其在控制鳃运动神经元迁移中具有细胞自主功能。
