Dynamic local mRNA localization and translation occurs during the postnatal molecular maturation of perivascular astrocytic processes
Astrocytes are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain's blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts aft...
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Published in | Glia Vol. 72; no. 4; pp. 777 - 793 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.04.2024
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Astrocytes are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain's blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts after birth and is essentially complete by postnatal day (P) 15. Progressive molecular maturation also occurs over this period, with the acquisition of proteins enriched in PvAPs. The mechanisms controlling the development and molecular maturation of PvAPs have not been extensively characterized. We reported previously that mRNAs are distributed unequally in mature PvAPs and are locally translated. Since dynamic mRNA localization and local translation influence the cell's polarity, we hypothesized that they might sustain the postnatal maturation of PvAPs. Here, we used a combination of molecular biology and imaging approaches to demonstrate that the development of PvAPs is accompanied by the transport of mRNA and polysomal mRNA into PvAPs, the development of a rough endoplasmic reticulum (RER) network and Golgi cisternae, and local translation. By focusing on genes and proteins that are selectively or specifically expressed in astrocytes, we characterized the developmental profile of mRNAs, polysomal mRNAs and proteins in PvAPs from P5 to P60. We found that some polysomal mRNAs polarized progressively towards the PvAPs. Lastly, we found that expression and localization of mRNAs in developing PvAPs is perturbed in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts. Our results indicate that dynamic mRNA localization and local translation influence the postnatal maturation of PvAPs.
Main Points
Development of perivascular astrocyte processes (PvAP) is accompanied by local translation.
mRNAs, polysomal mRNAs and proteins in PvAPs show different developmental profiles.
mRNA distribution in PvAPs is perturbed in Mlc1 KO mice. |
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Bibliography: | Katia Avila‐Gutierrez, Leila Slaoui, and Rodrigo Alvear‐Perez are co‐first authors. Anne‐Cécile Boulay and Martine Cohen‐Salmon are co‐last coauthors. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0894-1491 1098-1136 1098-1136 |
DOI: | 10.1002/glia.24503 |