Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool
| العنوان: | Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool |
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| المؤلفون: | Andrea Aguilar, Nathalie Spassky, Arturo Alvarez-Buylla, M. Romaguera Ros, José Manuel García-Verdugo, Young-Goo Han, L. Besse, Christine Laclef, Laetitia Strehl |
| المصدر: | DEVELOPMENTAL BIOLOGY r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) |
| بيانات النشر: | ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Cerebellum, Kinesins, Receptors, G-Protein-Coupled, Mice, Purkinje Cells, 0302 clinical medicine, Primary cilia, Sonic hedgehog, Promoter Regions, Genetic, Rhombic lip, Genetics, 0303 health sciences, education.field_of_study, Cilium, Stem Cells, joubert syndrome, Cerebellar development, Smoothened Receptor, Cell biology, neurogenesis, medicine.anatomical_structure, cerebellar development, embryonic structures, animal structures, Neurogenesis, Population, Mice, Transgenic, Biology, Kif3a, Article, 03 medical and health sciences, sonic hedgehog, primary cilia, Joubert syndrome, Glial Fibrillary Acidic Protein, medicine, Animals, Humans, KIF3A, Hedgehog Proteins, Cilia, education, Molecular Biology, 030304 developmental biology, Cell Biology, Granule cell, Mice, Inbred C57BL, biology.protein, Smoothened, 030217 neurology & neurosurgery, Developmental Biology |
| الوصف: | Cerebellar granule cell precursors (GCPs), which give rise to the most abundant neuronal type in the mammalian brain, arise from a restricted pool of primary progenitors in the rhombic lip (RL). Sonic hedgehog (Shh) secreted by developing Purkinje cells is essential for the expansion of GCPs and for cerebellar morphogenesis. Recent studies have shown that the primary cilium concentrates components of Shh signaling and that this structure is required for Shh signaling. GCPs have a primary cilium on their surface [Del Cerro, M.P., Snider, R.S. (1972). Studies on the developing cerebellum. II. The ultrastructure of the external granular layer. J Comp Neurol 144, 131-64.]. Here, we show that 1) this cilium can be conditionally ablated by crossing Kif3a(fl/-) mice with hGFAP-Cre mice, 2) removal of Kif3a from GCPs disrupts cerebellar development, and 3) these defects are due to a drastic reduction in Shh-dependent expansion of GCPs. A similar phenotype is observed when Smoothened (Smo), an essential transducer of Shh signaling, is removed from the same population of GCPs. Interestingly, Kif3a-Smo double conditional mutants show that Kif3a is epistatic to Smo. This work shows that Kif3a is essential for Shh-dependent expansion of cerebellar progenitors. Dysfunctional cilia are associated with diverse human disorders including Bardet-Biedl and Joubert syndromes. Cerebellar abnormalities observed in these patients could be explained by defects in Shh-induced GCP expansion. (C) 2008 Elsevier Inc. All rights reserved. |
| تدمد: | 0012-1606 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::caa02d4f3005700af09daea8282abe1dTest https://fundanet.cipf.es/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2927Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....caa02d4f3005700af09daea8282abe1d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00121606 |
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