Division of Neurogenetics and Cluster of Excellence Hearing4All, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
Research Center for Neurosensory Science, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
J Comp Neurol. 2021 Aug 1;529(11):3032-3045. doi: 10.1002/cne.25147. Epub 2021 Apr 8.
The dorsal cochlear nucleus (DCN) is a mammalian-specific nucleus of the auditory system. Anatomically, it is classified as a cerebellum-like structure. These structures are proposed to share genetic programs with the cerebellum. Previous analyses demonstrated that inhibitory serial sister cell types (SCTs) of the DCN and cerebellum are derived from the pancreatic transcription factor 1a (Ptf1a) lineage. Postmitotic neurons of the Ptf1a lineage often express the transcription factor Ladybird homeobox protein homolog 1 (Lbx1) which is involved in neuronal cell fate determination. Lbx1 is therefore an attractive candidate for a further component of the genetic program shared between the DCN and cerebellum. Here, we used cell-type specific marker analysis in combination with an Lbx1 reporter mouse line to analyze in both tissues which cell types of the Ptf1a lineage express Lbx1. In the DCN, stellate cells and Purkinje-like cartwheel cells were part of the Lbx1 lineage and Golgi cells were not, as determined by cell counts. In contrast, in the cerebellum, stellate cells and Golgi cells were part of the Lbx1 lineage and Purkinje cells were not. Hence, two out of three phenotypically similar cell types differed with respect to their Lbx1 expression. Our study demonstrates that Lbx1 is differentially recruited to the developmental genetic program of inhibitory neurons both within a given tissue and between the DCN and cerebellum. The differential expression of Lbx1 within the DCN and the cerebellum might contribute to the genetic individuation of the inhibitory SCTs to adapt to circuit specific tasks.
背侧耳蜗核（DCN）是听觉系统中哺乳动物特有的核团。从解剖学上看，它被归类为与小脑相似的结构。这些结构被认为与小脑共享遗传程序。之前的分析表明，DCN 和小脑的抑制性串联姐妹细胞类型（SCT）来自胰腺转录因子 1a（Ptf1a）谱系。Ptf1a 谱系的有丝分裂后神经元通常表达转录因子瓢虫同源盒蛋白 1（Lbx1），该蛋白参与神经元细胞命运决定。因此，Lbx1 是 DCN 和小脑之间共享遗传程序的进一步候选基因。在这里，我们使用细胞类型特异性标记分析结合 Lbx1 报告小鼠系，在这两种组织中分析 Ptf1a 谱系的哪些细胞类型表达 Lbx1。在 DCN 中，星形细胞和浦肯野样轮辐细胞是 Lbx1 谱系的一部分，而高尔基细胞不是，这是通过细胞计数确定的。相比之下，在小脑，星形细胞和高尔基细胞是 Lbx1 谱系的一部分，而浦肯野细胞不是。因此，在三种表型相似的细胞类型中，有两种在其 Lbx1 表达方面存在差异。我们的研究表明，Lbx1 在给定组织内以及 DCN 和小脑之间的抑制性神经元发育遗传程序中被差异招募。Lbx1 在 DCN 和小脑之间的差异表达可能有助于抑制性 SCT 适应特定电路任务的遗传个体化。
