Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
Development. 2015 Feb 1;142(3):522-32. doi: 10.1242/dev.115931. Epub 2015 Jan 6.
Cortical lamination is crucial for the assembly of cerebellar circuitry. In this process, granule neurons (GNs) migrate along Bergmann glia (BG), which are specialized astroglial cells, from the external granule layer to the internal granule layer. However, the molecular mechanisms underlying BG development are not well understood. Here, we show that GFAP::Cre;Erbb3(F/F) mice, which lack Erbb3 in both radial glia and neurons, exhibit impairments in balance and motor coordination. Cerebellar lamination is aberrant, with misplaced Purkinje neurons and GN clusters. These phenotypes were not observed in Math1::CreER(T2);Erbb3(F/F) mice, where the Erbb3 gene was deleted in GNs, suggesting involvement of non-neuronal Erbb3 in cerebellar lamination. Mechanistic studies indicate that ERBB3 is crucial for the proliferation of BG, which are required for GN migration. These observations identify a crucial role for ERBB3 in cerebellar lamination and reveal a novel mechanism that regulates BG development.
皮质分层对于小脑回路的组装至关重要。在此过程中，颗粒神经元 (GNs) 沿着 Bergmann 胶质（BG）从外颗粒层迁移到内颗粒层，BG 是专门的星形胶质细胞。然而，BG 发育的分子机制尚不清楚。在这里，我们展示了 GFAP::Cre;Erbb3(F/F) 小鼠，其在放射状胶质和神经元中均缺乏 Erbb3，表现出平衡和运动协调能力受损。小脑分层异常，浦肯野神经元和 GN 簇位置错误。这些表型在 Math1::CreER(T2);Erbb3(F/F) 小鼠中未观察到，其中 Erbb3 基因在 GNs 中缺失，表明非神经元 Erbb3 参与了小脑分层。机制研究表明，ERBB3 对于 BG 的增殖至关重要，而 BG 对于 GN 的迁移是必需的。这些观察结果确定了 ERBB3 在小脑分层中的关键作用，并揭示了调节 BG 发育的新机制。
