Lmx1a and Lmx1b are Redundantly Required for the Development of Multiple Components of the Mammalian Auditory System.
Lmx1a and Lmx1b are Redundantly Required for the Development of Multiple Components of the Mammalian Auditory System.
复制标题
DOI：
10.1016/j.neuroscience.2020.11.013
复制
发表时间：
2021-01-01
期刊：
影响因子：
3.3
通讯作者：
Fritzsch B
中科院分区：
文献类型：
--
作者：
Chizhikov VV;Iskusnykh IY;Fattakhov N;Fritzsch B
内耳、突起和脑干核是听觉和前庭系统的重要组成部分。人们认为，复杂系统的进化依赖于基因的复制。然而，重复基因对听觉或前庭系统发育的贡献却知之甚少。我们描述了Lmx1a和Lmx1b，它们起源于无脊椎动物Lmx1b样基因，冗余调节哺乳动物听觉/前庭系统的多个重要组成部分的发育。Lmx1a/b的缺失导致Corti内耳听觉器官消失，螺旋神经节受损，而在此之前，它们的关键调节因子Pax2的表达减少。其余内耳前庭器官的神经支配显示出不同寻常的大小或形状，与Lmx1a/b单基因突变相比，受影响更大。Lmx1a/b基因的个体缺失不会破坏脑干听核或内耳中央投射。然而，Lmx1a/b的联合缺失会消除耳蜗/前庭核中的兴奋性神经元，以及下菱形唇中它们的祖细胞中主调节因子Atoh1的表达。最后，在Lmx1a/b双突变体中，前庭传入神经异常地投射到顶板。这种表型与Wnt3a的表达改变有关，Wnt3a是Wnt通路的分泌配体，调节内耳突起的寻路。因此，Lmx1a/b对于哺乳动物内耳、内耳中央突起和耳蜗/前庭核的发育是冗余的。
The inner ear, projections, and brainstem nuclei are essential components of the auditory and vestibular systems. It is believed that the evolution of complex systems depends on duplicated sets of genes. The contribution of duplicated genes to auditory or vestibular system development, however, is poorly understood. We describe that Lmx1a and Lmx1b, which originate from the invertebrate Lmx1b-like gene, redundantly regulate development of multiple essential components of the mammalian auditory/vestibular systems. Combined, but not individual, loss of Lmx1a/b eliminated the auditory inner ear organ of Corti and disrupted the spiral ganglion, which was preceded by a diminished expression of their critical regulator Pax2. Innervation of the remaining inner ear vestibular organs revealed unusual sizes or shapes and was more affected compared to Lmx1a/b single-gene mutants. Individual loss of Lmx1a/b genes did not disrupt brainstem auditory nuclei or inner ear central projections. Combined loss of Lmx1a/b, however, eliminated excitatory neurons in cochlear/vestibular nuclei, and also the expression of a master regulator Atoh1 in their progenitors in the lower rhombic lip. Finally, in Lmx1a/b double mutants, vestibular afferents aberrantly projected to the roof plate. This phenotype was associated with altered expression of Wnt3a, a secreted ligand of the Wnt pathway that regulates pathfinding of inner ear projections. Thus, Lmx1a/b are redundantly required for the development of the mammalian inner ear, inner ear central projections, and cochlear/vestibular nuclei.
登录
查看更多内容
影响因子：
16.6
作者：
Chizhikov, Victor V.;Iskusnykh, Igor Y.;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
DOI：
10.1073/pnas.0910786107
发表时间：
2010-06-08
影响因子：
11.1
作者：
Chizhikov, Victor V.;Lindgren, Anne G.;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
影响因子：
4.6
作者：
Elliott, Karen L.;Fritzsch, Bernd
通讯作者：
Fritzsch, Bernd
影响因子：
4.6
作者：
Chizhikov, Victor V.;Lindgren, Anne G.;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
影响因子：
2.7
作者：
Fritzsch B;Elliott KL
通讯作者：
Elliott KL