Involvement of transcription factors in early motor neuron cell death in cervical segments of avian embryos

我们先前报道，早期鸟类胚胎中颈运动神经元的细胞死亡只发生在不表达LIM-HD转录因子成员Lim3的运动神经元(MN)亚群中。在本研究中，为了阐明决定细胞死亡的机制，我们阐明了颈髓和胸髓MNS亚型的发展。我们研究了MN的出生日期与其最终位置、详细的迁移模式以及LIM-HD转录因子(Isl1、Isl2和Lim3)和MNR2蛋白在鸡胚胎中的表达模式的变化之间的关系。然而，在MNS的亚群中，LIM3的表达在E4中丢失。在胸段，这个Lim3阴性的群体在支配肋间肌肉的内侧运动柱的外侧分支中变成了MN，而在颈髓，这个群体在E5因为细胞死亡而消失。这两个种群在相似的发育阶段成为有丝分裂后，并且位于运动神经元柱的相似区域。这种一致性表明，两个群体是相似的神经元群。由HOX转录因子的表达决定的脊髓肩尾分化的差异可能决定了这两个种群的不同命运。尽管我们探索了这种可能性，但在本研究项目期间，我们无法获得决定性的结果。

We previously reported that cell death of cervical motor neurons in early avian embryo occurs only in a subpopulation of motoneurons(MNs) that do not express Lim3, a member of LIM-HD transcription factors. In the present study, to elucidate mechanisms that determine cells to die, we clarified development of subtypes of MNs in the cervical and thoracic spinal cord. We examined correlations between birthdates of MNs and their final locations, detailed migration patterns, and change of expression patterns of LIM-HD transcription factors (Isl1, Isl2 and Lim3) and MNR2 protein in the chick embryo.Detailed analysis of expression patterns of Isl1, Isl2 and Lim3 and MNR2 revealed that these four marker proteins were once expressed by all motoneurons in both cervical and thoracic segments. However, Lim3 expression was lost in subpopulations of MNs by E4. In thoracic segments this Lim3-negative population became MNs in the lateral division of the medial motor column that innervate intercostal muscles, whereas in the cervical spinal cord this population disappeared by E5 because of cell death. Both populations became postmitotic in similar developmental stages and are located in similar regions of the motoneurons column. This consistency suggests that two populations are analogous neuronal groups. Difference of rostrocaudal differentiation of the spinal cord, which is determined by expression of Hox transcription factors, may determine different fates of the two populations.Although we pursued this possibility, we could not obtain decisive results within the period of this research project.