LIM Homeobox 4 (lhx4) regulates retinal neural differentiation and visual function in zebrafish

Rui Guo; Kangkang Ge; Yuying Wang; Minxia Lu; Fei Li; Lili Tian; Lin Gan; Donglai Sheng

doi:10.1038/s41598-021-81211-w

LIM Homeobox 4 (lhx4) regulates retinal neural differentiation and visual function in zebrafish

Rui Guo, Kangkang Ge, Yuying Wang, Minxia Lu, Fei Li, Lili Tian, Lin Gan, Donglai Sheng

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

LIM homeobox 4 (LHX4) is expressed in the photoreceptors (PRs) of the outer nuclear layer (ONL) and bipolar cells (BCs) of the inner nuclear layer (INL) in mouse and chicken retina. It regulates the subtype-specific development of rod BCs and cone BCs in the mouse retina. However, no report has been published on its expression and function in the zebrafish retina. In this study, we assessed the expression of Lhx4 using in situ hybridization (ISH) technique and explored its role in zebrafish (Danio rerio) retinal development via morpholino (MO) technology. We found that the expression of lhx4 in the zebrafish retina begins 48 h post-fertilization (hpf) and is continuously expressed in the ONL and INL. A zebrafish model constructed with lhx4 knockdown in the eyes through vivo-MO revealed that: lhx4 knockdown inhibits the differentiation of Parvalbumin⁺ amacrine cells (ACs) and Rhodopsin⁺ rod photoreceptors (RPs), enhances the expression of visual system homeobox 2 (vsx2); and damages the responses of zebrafish to light stimulus, without affecting the differentiation of OFF-BCs and rod BCs, and apoptosis in the retina. These findings reveal that lhx4 regulates neural differentiation in the retina and visual function during zebrafish embryonic development.

Original language	English (US)
Article number	1977
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-81211-w
State	Published - Dec 2021
Externally published	Yes

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title = "LIM Homeobox 4 (lhx4) regulates retinal neural differentiation and visual function in zebrafish",

abstract = "LIM homeobox 4 (LHX4) is expressed in the photoreceptors (PRs) of the outer nuclear layer (ONL) and bipolar cells (BCs) of the inner nuclear layer (INL) in mouse and chicken retina. It regulates the subtype-specific development of rod BCs and cone BCs in the mouse retina. However, no report has been published on its expression and function in the zebrafish retina. In this study, we assessed the expression of Lhx4 using in situ hybridization (ISH) technique and explored its role in zebrafish (Danio rerio) retinal development via morpholino (MO) technology. We found that the expression of lhx4 in the zebrafish retina begins 48 h post-fertilization (hpf) and is continuously expressed in the ONL and INL. A zebrafish model constructed with lhx4 knockdown in the eyes through vivo-MO revealed that: lhx4 knockdown inhibits the differentiation of Parvalbumin+ amacrine cells (ACs) and Rhodopsin+ rod photoreceptors (RPs), enhances the expression of visual system homeobox 2 (vsx2); and damages the responses of zebrafish to light stimulus, without affecting the differentiation of OFF-BCs and rod BCs, and apoptosis in the retina. These findings reveal that lhx4 regulates neural differentiation in the retina and visual function during zebrafish embryonic development.",

author = "Rui Guo and Kangkang Ge and Yuying Wang and Minxia Lu and Fei Li and Lili Tian and Lin Gan and Donglai Sheng",

note = "Funding Information: This work was supported by the Zhejiang Provincial Basic Public Welfare Research Plan of China (LY20H060003, LY20H090007); the Zhejiang Provincial Medical and Health Research Project of China (2015113063); and the Zhejiang Province Traditional Chinese Medicine Science and Technology Project Foundation (No. 2020ZQ001). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41598-021-81211-w",

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AU - Guo, Rui

AU - Ge, Kangkang

AU - Wang, Yuying

AU - Lu, Minxia

AU - Li, Fei

AU - Tian, Lili

AU - Gan, Lin

AU - Sheng, Donglai

N1 - Funding Information: This work was supported by the Zhejiang Provincial Basic Public Welfare Research Plan of China (LY20H060003, LY20H090007); the Zhejiang Provincial Medical and Health Research Project of China (2015113063); and the Zhejiang Province Traditional Chinese Medicine Science and Technology Project Foundation (No. 2020ZQ001). Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - LIM homeobox 4 (LHX4) is expressed in the photoreceptors (PRs) of the outer nuclear layer (ONL) and bipolar cells (BCs) of the inner nuclear layer (INL) in mouse and chicken retina. It regulates the subtype-specific development of rod BCs and cone BCs in the mouse retina. However, no report has been published on its expression and function in the zebrafish retina. In this study, we assessed the expression of Lhx4 using in situ hybridization (ISH) technique and explored its role in zebrafish (Danio rerio) retinal development via morpholino (MO) technology. We found that the expression of lhx4 in the zebrafish retina begins 48 h post-fertilization (hpf) and is continuously expressed in the ONL and INL. A zebrafish model constructed with lhx4 knockdown in the eyes through vivo-MO revealed that: lhx4 knockdown inhibits the differentiation of Parvalbumin+ amacrine cells (ACs) and Rhodopsin+ rod photoreceptors (RPs), enhances the expression of visual system homeobox 2 (vsx2); and damages the responses of zebrafish to light stimulus, without affecting the differentiation of OFF-BCs and rod BCs, and apoptosis in the retina. These findings reveal that lhx4 regulates neural differentiation in the retina and visual function during zebrafish embryonic development.

AB - LIM homeobox 4 (LHX4) is expressed in the photoreceptors (PRs) of the outer nuclear layer (ONL) and bipolar cells (BCs) of the inner nuclear layer (INL) in mouse and chicken retina. It regulates the subtype-specific development of rod BCs and cone BCs in the mouse retina. However, no report has been published on its expression and function in the zebrafish retina. In this study, we assessed the expression of Lhx4 using in situ hybridization (ISH) technique and explored its role in zebrafish (Danio rerio) retinal development via morpholino (MO) technology. We found that the expression of lhx4 in the zebrafish retina begins 48 h post-fertilization (hpf) and is continuously expressed in the ONL and INL. A zebrafish model constructed with lhx4 knockdown in the eyes through vivo-MO revealed that: lhx4 knockdown inhibits the differentiation of Parvalbumin+ amacrine cells (ACs) and Rhodopsin+ rod photoreceptors (RPs), enhances the expression of visual system homeobox 2 (vsx2); and damages the responses of zebrafish to light stimulus, without affecting the differentiation of OFF-BCs and rod BCs, and apoptosis in the retina. These findings reveal that lhx4 regulates neural differentiation in the retina and visual function during zebrafish embryonic development.

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LIM Homeobox 4 (lhx4) regulates retinal neural differentiation and visual function in zebrafish

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