Jarrar Wassan, Dias Jose M, Ericson Johan, Arnold Hans-Henning, Holz Andreas
Cell and Molecular Biology, Zoological Institute, University of Braunschweig, Braunschweig, Germany.
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
PLoS One. 2015 Apr 28;10(4):e0124408. doi: 10.1371/journal.pone.0124408. eCollection 2015.
Cranial motor nerves in vertebrates are comprised of the three principal subtypes of branchial, visceral, and somatic motor neurons, which develop in typical patterns along the anteroposterior and dorsoventral axes of hindbrain. Here we demonstrate that the formation of branchial and visceral motor neurons critically depends on the transcription factors Nkx2.2 and Nkx2.9, which together determine the cell fate of neuronal progenitor cells. Disruption of both genes in mouse embryos results in complete loss of the vagal and spinal accessory motor nerves, and partial loss of the facial and glossopharyngeal motor nerves, while the purely somatic hypoglossal and abducens motor nerves are not diminished. Cell lineage analysis in a genetically marked mouse line reveals that alterations of cranial nerves in Nkx2.2; Nkx2.9 double-deficient mouse embryos result from changes of cell fate in neuronal progenitor cells. As a consequence progenitors of branchiovisceral motor neurons in the ventral p3 domain of hindbrain are transformed to somatic motor neurons, which use ventral exit points to send axon trajectories to their targets. Cell fate transformation is limited to the caudal hindbrain, as the trigeminal nerve is not affected in double-mutant embryos suggesting that Nkx2.2 and Nkx2.9 proteins play no role in the development of branchiovisceral motor neurons in hindbrain rostral to rhombomere 4.
脊椎动物的颅运动神经由鳃运动神经元、内脏运动神经元和躯体运动神经元这三种主要亚型组成，它们沿着后脑的前后轴和背腹轴以典型模式发育。在这里，我们证明鳃运动神经元和内脏运动神经元的形成关键取决于转录因子Nkx2.2和Nkx2.9，它们共同决定神经元祖细胞的细胞命运。小鼠胚胎中这两个基因的破坏导致迷走神经和脊髓副运动神经完全缺失，以及面神经和舌咽运动神经部分缺失，而纯粹的躯体舌下神经和展神经则未减少。对一个基因标记的小鼠品系进行细胞谱系分析表明，Nkx2.2;Nkx2.9双缺陷小鼠胚胎中颅神经的改变是由神经元祖细胞的细胞命运变化引起的。因此，后脑腹侧p3区域的鳃内脏运动神经元祖细胞转变为躯体运动神经元，这些神经元利用腹侧出口点将轴突轨迹发送到它们的靶标。细胞命运转变仅限于后脑尾部，因为三叉神经在双突变胚胎中不受影响，这表明Nkx2.2和Nkx2.9蛋白在菱脑节4前方的后脑鳃内脏运动神经元发育中不起作用。
