The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina

Yoshimoto, Takuya; Chaya, Taro; Varner, Leah R.; Ando, Makoto; Tsujii, Toshinori; Motooka, Daisuke; Kimura, Kazuhiro; Furukawa, Takahisa

doi:https://doi.org/10.1016/j.jbc.2023.105461

The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina

Yoshimoto, Takuya; Chaya, Taro; Varner, Leah R. et al.

Journal of Biological Chemistry, 2023, 299(12), 105461

Number of Access:836（2025-08-18 20:51 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93380

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Title	The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina
Creator	CreatorName Yoshimoto, Takuya
	NRID 1000050747087 1000050747087 researchmap permalink chaya chaya Scopus Author ID 37094720600 37094720600 CreatorName Chaya, Taro
	CreatorName Varner, Leah R.
	CreatorName Ando, Makoto
	CreatorName Tsujii, Toshinori
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 CreatorName Motooka, Daisuke
	NRID 1000060335255 1000060335255 CreatorName Kimura, Kazuhiro
	NRID 1000050260609 1000050260609 researchmap permalink read0083689 read0083689 Scopus Author ID 7403160171 7403160171 ORCID 0000-0003-4171-220X 0000-0003-4171-220X CreatorName Furukawa, Takahisa
Subject	homeostasis
	inflammation
	Müller glial cell
	retina
	transcription factor
Description	Yoshimoto T., Chaya T., Varner L.R., et al. The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina. Journal of Biological Chemistry 299, 105461 (2023); https://doi.org/10.1016/j.jbc.2023.105461.
Abstract	Müller glial cells, which are the most predominant glial subtype in the retina, play multiple important roles, including the maintenance of structural integrity, homeostasis, and physiological functions of the retina. We have previously found that the Rax homeoprotein is expressed in postnatal and mature Müller glial cells in the mouse retina. However, the function of Rax in postnatal and mature Müller glial cells remains to be elucidated. In the current study, we first investigated Rax function in retinal development using retroviral lineage analysis and found that Rax controls the specification of late-born retinal cell types, including Müller glial cells in the postnatal retina. We next generated Rax tamoxifen–induced conditional KO (Rax iCKO) mice, where Rax can be depleted in mTFP-labeled Müller glial cells upon tamoxifen treatment, by crossing Raxflox/flox mice with Rlbp1-CreERT2 mice, which we have produced. Immunohistochemical analysis showed a characteristic of reactive gliosis and enhanced gliosis of Müller glial cells in Rax iCKO retinas under normal and stress conditions, respectively. We performed RNA-seq analysis on mTFP-positive cells purified from the Rax iCKO retina and found significantly reduced expression of suppressor of cytokine signaling-3 (Socs3). Reporter gene assays showed that Rax directly transactivates the Socs3 promoter. We observed decreased expression of Socs3 in Müller glial cells of Rax iCKO retinas by immunostaining. Taken together, the present results suggest that Rax suppresses inflammation in Müller glial cells by transactivating Socs3. This study sheds light on the transcriptional regulatory mechanisms underlying retinal Müller glial cell homeostasis.
Publisher	American Society for Biochemistry and Molecular Biology Inc.
Source Title	Journal of Biological Chemistry
Volume (Issue)	299(12)
Page	105461
Date of Issued	2023-12-01
Language	English
Handle URL	https://hdl.handle.net/11094/93380
PISSN	00219258
eISSN	1083351X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.jbc.2023.105461
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2023, 299(12), p. 105461
DC.title	The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina
DC.creator	Yoshimoto, Takuya
	Chaya, Taro
	Varner, Leah R.
	Ando, Makoto
	Tsujii, Toshinori
	Motooka, Daisuke
	Kimura, Kazuhiro
	Furukawa, Takahisa
DC.publisher	American Society for Biochemistry and Molecular Biology Inc.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-12-01
DC.identifier	https://doi.org/10.1016/j.jbc.2023.105461
DC.subject	homeostasis
	inflammation
	Müller glial cell
	retina
	transcription factor
DC.description	Yoshimoto T., Chaya T., Varner L.R., et al. The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina. Journal of Biological Chemistry 299, 105461 (2023); https://doi.org/10.1016/j.jbc.2023.105461.
DCTERMS.abstract	Müller glial cells, which are the most predominant glial subtype in the retina, play multiple important roles, including the maintenance of structural integrity, homeostasis, and physiological functions of the retina. We have previously found that the Rax homeoprotein is expressed in postnatal and mature Müller glial cells in the mouse retina. However, the function of Rax in postnatal and mature Müller glial cells remains to be elucidated. In the current study, we first investigated Rax function in retinal development using retroviral lineage analysis and found that Rax controls the specification of late-born retinal cell types, including Müller glial cells in the postnatal retina. We next generated Rax tamoxifen–induced conditional KO (Rax iCKO) mice, where Rax can be depleted in mTFP-labeled Müller glial cells upon tamoxifen treatment, by crossing Raxflox/flox mice with Rlbp1-CreERT2 mice, which we have produced. Immunohistochemical analysis showed a characteristic of reactive gliosis and enhanced gliosis of Müller glial cells in Rax iCKO retinas under normal and stress conditions, respectively. We performed RNA-seq analysis on mTFP-positive cells purified from the Rax iCKO retina and found significantly reduced expression of suppressor of cytokine signaling-3 (Socs3). Reporter gene assays showed that Rax directly transactivates the Socs3 promoter. We observed decreased expression of Socs3 in Müller glial cells of Rax iCKO retinas by immunostaining. Taken together, the present results suggest that Rax suppresses inflammation in Müller glial cells by transactivating Socs3. This study sheds light on the transcriptional regulatory mechanisms underlying retinal Müller glial cell homeostasis.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93380
citation_title	The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina
citation_author	Yoshimoto, Takuya
	Chaya, Taro
	Varner, Leah R.
	Ando, Makoto
	Tsujii, Toshinori
	Motooka, Daisuke
	Kimura, Kazuhiro
	Furukawa, Takahisa
citation_publisher	American Society for Biochemistry and Molecular Biology Inc.
citation_language	English
citation_date	2023-12-01
citation_journal_title	Journal of Biological Chemistry
citation_volume	299
citation_issue	12
citation_firstpage	105461
citation_doi	https://doi.org/10.1016/j.jbc.2023.105461
citation_public_url	https://hdl.handle.net/11094/93380

The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina

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