Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma
Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma
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DOI：
10.1007/s10571-016-0354-3
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Tocchini-Valentini, Glauco P.
中科院分区：
文献类型：
--
作者：
Di Pietro, Chiara;Marazziti, Daniela;Tocchini-Valentini, Glauco P.
细胞初级纤毛至关重要地感知和转导细胞外的物理化学刺激。纤毛介导的发育信号传导是组织和细胞类型特异性的。初级纤毛是小脑分化和神经元颗粒前体的声波刺猬 (Shh) 依赖性增殖所必需的。哺乳动物G蛋白偶联受体37-like 1在小脑伯格曼胶质细胞星形胶质细胞中特异性表达，参与调节出生后小脑颗粒神经元增殖/分化以及伯格曼胶质细胞和浦肯野神经元成熟。小鼠受体蛋白与纤毛相关 Shh 受体复合物的 patched 1 成分相互作用。带有补丁同源物 1 突变的杂合小鼠，就像带有补丁 1 杂合子的人类一样，Shh 亚组髓母细胞瘤 (MB) 和其他肿瘤的发病率较高。在两种具有改变的Shh信号传导的小鼠品系中，在出生后发育和成年期间鉴定出具有初级纤毛的小脑细胞：G蛋白偶联受体37样1无效突变体和MB敏感的杂合补丁同源物1突变体。除了颗粒神经元和浦肯野神经元之外，从出生到成年的野生型和突变动物中，伯格曼胶质星形胶质细胞也表达初级纤毛。纤毛数量和长度的变化与出生后小脑发育过程中神经元和胶质细胞增殖和成熟的不同水平有关。在杂合补丁同源物 1 突变小鼠的肿瘤前 MB 病变中也检测到了初级纤毛，它们可以代表用于开发和分析新型小脑致癌模型的特定标记。
Cellular primary cilia crucially sense and transduce extracellular physicochemical stimuli. Cilium-mediated developmental signaling is tissue and cell type specific. Primary cilia are required for cerebellar differentiation and sonic hedgehog (Shh)-dependent proliferation of neuronal granule precursors. The mammalian G-protein-coupled receptor 37-like 1 is specifically expressed in cerebellar Bergmann glia astrocytes and participates in regulating postnatal cerebellar granule neuron proliferation/differentiation and Bergmann glia and Purkinje neuron maturation. The mouse receptor protein interacts with the patched 1 component of the cilium-associated Shh receptor complex. Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors. Cerebellar cells bearing primary cilia were identified during postnatal development and in adulthood in two mouse strains with altered Shh signaling: a G-protein-coupled receptor 37-like 1 null mutant and an MB-susceptible, heterozygous patched homolog 1 mutant. In addition to granule and Purkinje neurons, primary cilia were also expressed by Bergmann glia astrocytes in both wild-type and mutant animals, from birth to adulthood. Variations in ciliary number and length were related to the different levels of neuronal and glial cell proliferation and maturation, during postnatal cerebellar development. Primary cilia were also detected in pre-neoplastic MB lesions in heterozygous patched homolog 1 mutant mice and they could represent specific markers for the development and analysis of novel cerebellar oncogenic models.