Identification of an early subset of cerebellar nuclei neurons in mice

Author:

Rahimi-Balaei Maryam12,Amiri Shayan13,Lamonerie Thomas4,Wu Sih-Rong567,Zoghbi Huda Y678,Consalez G Giacomo910,Goldowitz Daniel2,Marzban Hassan1ORCID

Affiliation:

1. Department of Human Anatomy and Cell Science, The Children’s Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

2. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, University of British Columbia

3. Department of Pharmacology and Therapeutics, Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, University of Manitoba

4. Université Côte d’Azur, CNRS, Inserm, iBV

5. University of California San Francisco (UCSF)

6. Department of Neuroscience, Baylor College of Medicine

7. Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital

8. Howard Hughes Medical Institute, Baylor College of Medicine

9. Division of Neuroscience, IRCCS Ospedale san Raffaele

10. Università Vita-Salute San Raffaele

Abstract

Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium. Embryos were collected at early stages of development and processed for immunohistochemistry (IHC), Western blotting, in situ hybridization (ISH), embryonic culture, DiI labeling, and flow cytometry analysis (FCM). Our findings indicate that a subset of CN neurons expressing α-synuclein (SNCA), OTX2, MEIS2, and p75NTR (NGFR) are located in the rostro-ventral (rv) region of the nuclear transitory zone (NTZ), while CN neurons derived from the rhombic lip are positioned in the caudo-dorsal (cd) area of the NTZ in the cerebellar primordium. Utilizing Otx2-GFP and Atoh1 −/− mice, we have determined that these cells do not originate from the germinal zone of the cerebellar primordium. These results suggest the existence of a novel extrinsic germinal zone for the cerebellar primordium, possibly the mesencephalon, from which early CN neurons originate.

Publisher

eLife Sciences Publications, Ltd

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