Studer M, Lumsden A, Ariza-McNaughton L, Bradley A, Krumlauf R
Division of Developmental Neurobiology, MRC National Institute for Medical Research, Mill Hill, London, UK.
Nature. 1996;384(6610):630-4. doi: 10.1038/384630a0.
Segmentation of the vertebrate hindbrain into rhombomeres is important for the anterior-posterior arrangement of cranial motor nuclei and efferent nerves. Underlying this reiterated organization, Hox genes display segmentally restricted domains of expression, such as expression of Hoxb-1 (refs 5, 6) in rhombomere 4 (r4). Here we report that absence of Hoxb-1 leads to changes in r4 identity. In mutant mouse embryos, molecular markers indicate that patterning of r4 is initiated properly but not maintained. Cellular analysis by DiI tracing reveals that the r4-specific facial branchiomotor (FBM) and contralateral vestibuloacoustic efferent (CVA) neurons are incorrectly specified. In wild-type mice CVA neurons migrate from r4 into the contralateral side, and we found in lineage analysis that FBM neurons migrate from r4 into r5. In mutants, motor neurons differentiate but the CVA and FBM neurons fail to migrate into their proper positions. Instead, they form a motor nucleus which migrates atypically, and there is a subsequent loss of the facial motor nerve. These results demonstrate that, as a part of its role in maintaining rhombomere identity, Hoxb-1 is involved in controlling migratory properties of motor neurons in the hindbrain.
脊椎动物后脑分割成菱脑节对于颅运动核和传出神经的前后排列很重要。在这种重复组织的基础下，Hox基因表现出分段受限的表达域，例如Hoxb-1（参考文献5、6）在菱脑节4（r4）中的表达。我们在此报告，Hoxb-1的缺失会导致r4身份的改变。在突变小鼠胚胎中，分子标记表明r4的模式形成起始正常，但未得到维持。通过DiI示踪进行的细胞分析显示，r4特异性的面鳃运动（FBM）神经元和对侧前庭听觉传出（CVA）神经元指定错误。在野生型小鼠中，CVA神经元从r4迁移到对侧，并且我们在谱系分析中发现FBM神经元从r4迁移到r5。在突变体中，运动神经元分化，但CVA和FBM神经元未能迁移到其正确位置。相反，它们形成了一个非典型迁移的运动核，随后面神经运动神经缺失。这些结果表明，作为其维持菱脑节身份作用的一部分，Hoxb-1参与控制后脑运动神经元的迁移特性。
