Dataset Information

M⁶A regulation of cortical and retinal neurogenesis is mediated by the redundant m⁶A readers YTHDFs.

ABSTRACT: m⁶A modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic m⁶A readers, YTHDF1, YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate that Ythdf1 and Ythdf2 double deletion but not individual knockout recapitulates the phenotype of Mettl14 knockout in cortex. In addition, we find that Mettl14 knockout in retina causes protracted proliferation of retinal progenitors, decreased numbers of retinal neurons, and disturbed laminar structure. This phenotype is only reproduced when Ythdf1, Ythdf2, and Ythdf3 are knocked out simultaneously in retina. Analysis of YTHDF target mRNAs in mouse cortex and retina reveals abundant overlapping mRNAs related to neurogenesis that are recognized and regulated by both YTHDF1 and YTHDF2. Together our results demonstrate that the functionally redundant YTHDFs mediate m⁶A regulation of cortical and retinal neurogenesis.

SUBMITTER: Niu F

PROVIDER: S-EPMC9418916 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

m6A regulation of cortical and retinal neurogenesis is mediated by the redundant m6A readers YTHDFs.

Niu Fugui F Che Pengfei P Yang Zhuoxuan Z Zhang Jian J Yang Lixin L Zhuang Mengru M Ou Xijun X Ji Sheng-Jian SJ

iScience 20220811 9

m6A modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic m6A readers, YTHDF1, YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate that Ythdf1 and Ythdf2 double deletion but not individual knockout recapitulates the phenotype of Mettl14 knockout in cortex. In addition, we find that Mettl14 knockout in retina causes protracted proliferation of retinal ...[more]

PMID: 36039295

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Project description:Purpose: Neuropeptide signaling has been reported to impact neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents in ex vivo preparations, and in vivo evidence for their developmental function is generally lacking. The goal of this study is to identify the impact of somatostatin signaling on retinal neurogenesis and development both ex vivo and in vivo. Methods: Mouse retinal explants grown ex vivo from E14-P0 and treated with a range of doses of agonist for the somatostatin receptor Sstr2 were multiplexed according to the MULTI-seq protocol and used to generate a single scRNA-seq expression library. Retinas from P0 littermates representing an allelic series (+/+, +/-, -/-) of Sstr2 KO mice were mutliplexed according to the MULTI-seq protocol and used to generate a single scRNA-seq expression library. Retinas from P14 littermates representing an allelic series (+/+, +/-, -/-) of Sstr2 KO mice were mutliplexed according to the MULTI-seq protocol and used to generate a single scRNA-seq expression library. Sequencing was performed on an illumina sequencer. Bcl files were analyzed by Cellranger. Samples were deconvoluted with the deMULTIplex r package and clustering and gene expression analysis were performed with the Seurat and Monocle2 r packages. Results: Cell type proportions were found to be impacted by Sstr2 signaling ex vivo with increasing levels of Sstr2 agonist found to decrease photoreceptor proportion and increase primary progenitor proportion. Sstr2 KO was not found to have an impact on cell type proportion in vivo at either P0 or P14. Sstr2 pharmacologic manipulation and Sstr2 KO did produce complementary gene expression changes in neurogenic progenitors indicating that somatostatin signaling downregulates neurogenesis. Conclusions: Our study demonstrates a role for somatostatin in retinal development by downregulating neurogenesis in neurogenic progenitors. However, it also demonstrates that somatostatin signaling is dispensable for in vivo retinal development and likely redundant with other cell extrinsic signals released during the same period.

Dataset Information

M⁶A regulation of cortical and retinal neurogenesis is mediated by the redundant m⁶A readers YTHDFs.

Publications

m<sup>6</sup>A regulation of cortical and retinal neurogenesis is mediated by the redundant m<sup>6</sup>A readers YTHDFs.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

M6A regulation of cortical and retinal neurogenesis is mediated by the redundant m6A readers YTHDFs.

Publications

m<sup>6</sup>A regulation of cortical and retinal neurogenesis is mediated by the redundant m<sup>6</sup>A readers YTHDFs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A regulation of cortical and retinal neurogenesis is mediated by the redundant m⁶A readers YTHDFs.