Nests of dividing neuroblasts sustain interneuron production for the developing human brain

Author:

Paredes Mercedes F.1234ORCID,Mora Cristina5ORCID,Flores-Ramirez Quetzal1ORCID,Cebrian-Silla Arantxa26ORCID,Del Dosso Ashley5,Larimer Phil1ORCID,Chen Jiapei35ORCID,Kang Gugene46ORCID,Gonzalez Granero Susana7ORCID,Garcia Eric1,Chu Julia1,Delgado Ryan2ORCID,Cotter Jennifer A.8ORCID,Tang Vivian5ORCID,Spatazza Julien6,Obernier Kirsten6ORCID,Ferrer Lozano Jaime9ORCID,Vento Maximo1011ORCID,Scott Julia12ORCID,Studholme Colin131415ORCID,Nowakowski Tomasz J.216,Kriegstein Arnold R.1234ORCID,Oldham Michael C.456ORCID,Hasenstaub Andrea17ORCID,Garcia-Verdugo Jose Manuel7ORCID,Alvarez-Buylla Arturo2346ORCID,Huang Eric J.2345ORCID

Affiliation:

1. Department of Neurology, University of California, San Francisco, CA 94143, USA.

2. Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, CA 94143, USA.

3. Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, USA.

4. Developmental and Stem Cell Graduate Program, University of California, San Francisco, CA 94143, USA.

5. Department of Pathology, University of California, San Francisco, CA 94143, USA.

6. Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.

7. Laboratorio de Neurobiología Comparada, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València–Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Valencia, Spain.

8. Department of Pathology, Children’s Hospital Los Angeles, and Keck School of Medicine of University of Southern California, Los Angeles, CA 90027, USA.

9. Department of Pathology, Hospital Universitari i Politecnic La Fe, Valencia, Spain.

10. Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain.

11. Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain.

12. Department of Bioengineering, Santa Clara University, Santa Clara, CA 95053, USA.

13. Biomedical Image Computing Group, Departments of Pediatrics, Bioengineering, and Radiology, University of Washington, Seattle, WA 98195, USA.

14. Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

15. Department of Radiology, University of Washington, Seattle, WA 98195, USA.

16. Department of Anatomy and Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA 94143, USA.

17. Department of Otolaryngology, University of California, San Francisco, CA 94143, USA.

Abstract

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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