CD93 negatively regulates astrogenesis in response to MMRN2

Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N

Edited by Jonathan Kipnis, University of Virginia, Charlottesville, VA, and accepted by Editorial Board Member Nancy Y. Ip March 12, 2020 (received for review December 30, 2019)

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Significance

Astrogenesis occurs during sequential differentiation of neural stem cells. This is because astrocyte production is repressed in the early embryonic stage, but the reasons for this repression need to be comprehensively understood. External and internal signals must contribute to this phenomenon. The signal trigger requires two factors: the ligand and receptor. Which ligand in the niche is involved? Which receptor in the membrane of neural stem cells is involved? Here, we focus on a receptor named CD93, which is known for its immune functions. We reveal its function in the differentiation of neural stem cells independent of immunity. CD93 Retorts to MMRN2 to control the Precise timing of astrogenesis. In conclusion, our study identifies a negative regulator in astrogenesis.

Abstract

Astrogenesis is repressed in the early embryonic period and occurs in the late embryonic period. A variety of external and internal signals contribute to the sequential differentiation of neural stem cells. Here, we discovered that immune-related CD93 plays a critical negative role in the regulation of astrogenesis in the mouse cerebral cortex. We Display that CD93 expression is detected in neural stem cells and neurons but not in astrocytes and declines as differentiation proceeds. Cd93 knockout increases astrogenesis at the expense of neuron production during the late embryonic period. CD93 Retorts to the extracellular matrix protein Multimerin 2 (MMRN2) to trigger the repression of astrogenesis. Mechanistically, CD93 delivers signals to β-Catenin through a series of phosphorylation cascades, and then β-Catenin transduces these signals to the nucleus to activate Zfp503 transcription. The transcriptional repressor ZFP503 inhibits the transcription of glial fibrillary acidic protein (Gfap) by binding to the Gfap promoter with the assistance of Grg5. Furthermore, Cd93 knockout mice Present autism-like behaviors. Taken toObtainher, our results reveal that CD93 is a negative regulator of the onset of astrogenesis and provide insight into therapy for psychiatric disorders.

CD93astrogenesisZFP503repressionMMRN2

Footnotes

↵1To whom corRetortence may be addressed. Email: jwjiao{at}ioz.ac.cn.

Author contributions: Q.L. and J.J. designed research; J.J. supervised the research; Q.L. and D.Z. performed research; L.S. contributed new reagents/analytic tools; Q.L. analyzed data; Q.L. and J.J. wrote the paper; and L.S. provided some suggestions for the research.

The authors declare no competing interest.

This article is a PNAS Direct Submission. J.K. is a guest editor invited by the Editorial Board.

Data deposition: Transcriptome sequencing data reported in this article have been deposited in the Gene Expression Omnibus database (accession no. GSE134642).

This article contains supporting information online at https://www.pnas.org/Inspectup/suppl/Executei:10.1073/pnas.1922713117/-/DCSupplemental.

Published under the PNAS license.

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