Microglia: An Intrinsic Component of the Proliferative Zones in the Fetal Rhesus Monkey (Macaca mulatta) Cerebral Cortex

Author:

Barger Nicole1,Keiter Janet2,Kreutz Anna2,Krishnamurthy Anjana1,Weidenthaler Cody2,Martínez-Cerdeño Verónica345,Tarantal Alice F678,Noctor Stephen C15

Affiliation:

1. Department of Psychiatry and Behavioral Sciences, School of Medicine, UC Davis, Sacramento, CA, USA

2. Neuroscience Graduate Program, UC Davis, Davis, CA, USA

3. Department of Pathology and Laboratory Medicine, School of Medicine, UC Davis, Sacramento, CA, USA

4. Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, CA, USA

5. MIND Institute, School of Medicine, UC Davis, Sacramento, CA, USA

6. Department of Pediatrics, School of Medicine, UC Davis, Sacramento, CA, USA

7. Department of Cell Biology and Human Anatomy, School of Medicine, UC Davis, Davis, CA, USA

8. California National Primate Research Center and Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases, UC Davis, Davis, CA, USA

Abstract

Abstract Microglial cells are increasingly recognized as modulators of brain development. We previously showed that microglia colonize the cortical proliferative zones in the prenatal brain and regulate the number of precursor cells through phagocytosis. To better define cellular interactions between microglia and proliferative cells, we performed lentiviral vector-mediated intraventricular gene transfer to induce enhanced green fluorescent protein expression in fetal cerebrocortical cells. Tissues were collected and counterstained with cell-specific markers to label microglial cells and identify other cortical cell types. We found that microglial cells intimately interact with the radial glial scaffold and make extensive contacts with neural precursor cells throughout the proliferative zones, particularly in the rhesus monkey fetus when compared to rodents. We also identify a subtype of microglia, which we term ‘periventricular microglia’, that interact closely with mitotic precursor cells in the ventricular zone. Our data suggest that microglia are structural modulators that facilitate remodeling of the proliferative zones as precursor cells migrate away from the ventricle and may facilitate the delamination of precursor cells. Taken together, these results indicate that microglial cells are an integral component of cortical proliferative zones and contribute to the interactive milieu in which cortical precursor cells function.

Funder

National Institutes of Health

MIND

Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases

California National Primate Research Center

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Cognitive Neuroscience

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