Origin of Climbing Fiber Neurons and Their Developmental Dependence onPtf1a
| Autor: | Tomoyuki Fujiyama, Mikio Hoshino, Mayumi Yamada, Toshio Terashima, Yoshiya Kawaguchi, Yo-ichi Nabeshima, Mami Terao |
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| Rok vydání: | 2007 |
| Předmět: |
Neurons
General Neuroscience Glutamic Acid Cell Differentiation Hindbrain General Medicine Articles Climbing fiber Cell fate determination Biology Embryonic stem cell Cell biology Rhombencephalon Neuroepithelial cell medicine.anatomical_structure nervous system Inferior olivary nucleus medicine Animals Mossy fiber (cerebellum) Neuron Transcription factor Neuroscience gamma-Aminobutyric Acid Transcription Factors |
| Zdroj: | The Journal of Neuroscience. 27:10924-10934 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1423-07.2007 |
| Popis: | Climbing fiber (CF) neurons in the inferior olivary nucleus (ION) extend their axons to Purkinje cells, playing a crucial role in regulating cerebellar function. However, little is known about their precise place of birth and developmental molecular machinery. Here, we describe the origin of the CF neuron lineage and the involvement ofPtf1a(pancreatic transcription factor 1a) in CF neuron development. Ptf1a protein was found to be expressed in a discrete dorsolateral region of the embryonic caudal hindbrain neuroepithelium. Because expression of Ptf1a is not overlapping other transcription factors such as Math1 (mouse atonal homolog 1) and Neurogenin1, which are suggested to define domains within caudal hindbrain neuroepithelium (Landsberg et al., 2005), we named the neuroepithelial region the Ptf1a domain. Analysis of mice that express β-galactosidase from thePtf1alocus revealed that CF neurons are derived from the Ptf1a domain. In contrast, retrograde labeling of precerebellar neurons indicated that mossy fiber neurons are not derived from Ptf1a-expressing progenitors. We could observe a detailed migratory path of CF neurons from the Ptf1a domain to the ION during embryogenesis. InPtf1anull mutants, putative immature CF neurons produced from this domain were unable to migrate or differentiate appropriately, resulting in a failure of ION formation. Apoptotic cells were observed in the mutant hindbrain. Furthermore, the fate of some cells in thePtf1alineage were changed to mossy fiber neurons inPtf1anull mutants. These findings clarify the precise origin of CF neurons and suggest thatPtf1acontrols their fate, survival, differentiation, and migration during development. |
| Databáze: | OpenAIRE |
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