Visuomotor anomalies in achiasmatic mice expressing a transfer-defective Vax1 mutant

Kwang Wook Min; Namsuk Kim; Jae Hoon Lee; Younghoon Sung; Museong Kim; Eun Jung Lee; Jong Myeong Kim; Jae Hyun Kim; Jaeyoung Lee; Wonjin Cho; Jee Myung Yang; Nury Kim; Jaehoon Kim; C. Justin Lee; Young Gyun Park; Seung Hee Lee; Han Woong Lee; Jin Woo Kim

doi:10.1038/s12276-023-00930-4

Visuomotor anomalies in achiasmatic mice expressing a transfer-defective Vax1 mutant

Kwang Wook Min, Namsuk Kim, Jae Hoon Lee, Younghoon Sung, Museong Kim, Eun Jung Lee, Jong Myeong Kim, Jae Hyun Kim, Jaeyoung Lee, Wonjin Cho, Jee Myung Yang, Nury Kim, Jaehoon Kim, C. Justin Lee, Young Gyun Park, Seung Hee Lee, Han Woong Lee, Jin Woo Kim

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

Abstract

In binocular animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to the formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1^AA/AA mice expressing the Vax1^AA mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1^AA protein from the Vax1^AA/AA mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1^AA/AA mice connect exclusively to ipsilateral brain areas after failing to access the midline, resulting in reduced visual acuity and abnormal oculomotor responses. Overall, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the bilateral RGC axon projection in proper visuomotor responses.

Original language	English
Pages (from-to)	385-400
Number of pages	16
Journal	Experimental and Molecular Medicine
Volume	55
Issue number	2
DOIs	https://doi.org/10.1038/s12276-023-00930-4
Publication status	Published - 2023 Feb

Bibliographical note

Funding Information:
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES)—Finance Code 001.

Funding Information:
We thank Ilsong Choi and Anna Shin for helping with the mouse ocular behavioral tests. This work was supported by National Research Foundation of Korea (NRF) grants (NRF-2022R1A2C3003589; NRF-2018R1A5A1024261) funded by the Korean Ministry of Science and ICT (MSIT) and an International Collaboration Initiative grant (KAIST-N11210255) supported by KAIST, South Korea. This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Korean Ministry of Agriculture, Food, and Rural Affairs. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#13-130) of Korea Advanced Institute of Science and Technology.

Publisher Copyright:
© 2023, The Author(s).

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry

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Cite this

Min, K. W., Kim, N., Lee, J. H., Sung, Y., Kim, M., Lee, E. J., Kim, J. M., Kim, J. H., Lee, J., Cho, W., Yang, J. M., Kim, N., Kim, J., Lee, C. J., Park, Y. G., Lee, S. H., Lee, H. W., & Kim, J. W. (2023). Visuomotor anomalies in achiasmatic mice expressing a transfer-defective Vax1 mutant. Experimental and Molecular Medicine, 55(2), 385-400. https://doi.org/10.1038/s12276-023-00930-4

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title = "Visuomotor anomalies in achiasmatic mice expressing a transfer-defective Vax1 mutant",

abstract = "In binocular animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to the formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from the Vax1AA/AA mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas after failing to access the midline, resulting in reduced visual acuity and abnormal oculomotor responses. Overall, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the bilateral RGC axon projection in proper visuomotor responses.",

author = "Min, {Kwang Wook} and Namsuk Kim and Lee, {Jae Hoon} and Younghoon Sung and Museong Kim and Lee, {Eun Jung} and Kim, {Jong Myeong} and Kim, {Jae Hyun} and Jaeyoung Lee and Wonjin Cho and Yang, {Jee Myung} and Nury Kim and Jaehoon Kim and Lee, {C. Justin} and Park, {Young Gyun} and Lee, {Seung Hee} and Lee, {Han Woong} and Kim, {Jin Woo}",

note = "Funding Information: This study was financed in part by the Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior – Brasil (CAPES)—Finance Code 001. Funding Information: We thank Ilsong Choi and Anna Shin for helping with the mouse ocular behavioral tests. This work was supported by National Research Foundation of Korea (NRF) grants (NRF-2022R1A2C3003589; NRF-2018R1A5A1024261) funded by the Korean Ministry of Science and ICT (MSIT) and an International Collaboration Initiative grant (KAIST-N11210255) supported by KAIST, South Korea. This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Korean Ministry of Agriculture, Food, and Rural Affairs. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#13-130) of Korea Advanced Institute of Science and Technology. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

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doi = "10.1038/s12276-023-00930-4",

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volume = "55",

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AU - Min, Kwang Wook

AU - Kim, Namsuk

AU - Lee, Jae Hoon

AU - Sung, Younghoon

AU - Kim, Museong

AU - Lee, Eun Jung

AU - Kim, Jong Myeong

AU - Kim, Jae Hyun

AU - Lee, Jaeyoung

AU - Cho, Wonjin

AU - Yang, Jee Myung

AU - Kim, Nury

AU - Kim, Jaehoon

AU - Lee, C. Justin

AU - Park, Young Gyun

AU - Lee, Seung Hee

AU - Lee, Han Woong

AU - Kim, Jin Woo

N1 - Funding Information: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES)—Finance Code 001. Funding Information: We thank Ilsong Choi and Anna Shin for helping with the mouse ocular behavioral tests. This work was supported by National Research Foundation of Korea (NRF) grants (NRF-2022R1A2C3003589; NRF-2018R1A5A1024261) funded by the Korean Ministry of Science and ICT (MSIT) and an International Collaboration Initiative grant (KAIST-N11210255) supported by KAIST, South Korea. This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Korean Ministry of Agriculture, Food, and Rural Affairs. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#13-130) of Korea Advanced Institute of Science and Technology. Publisher Copyright: © 2023, The Author(s).

PY - 2023/2

Y1 - 2023/2

N2 - In binocular animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to the formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from the Vax1AA/AA mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas after failing to access the midline, resulting in reduced visual acuity and abnormal oculomotor responses. Overall, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the bilateral RGC axon projection in proper visuomotor responses.

AB - In binocular animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to the formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from the Vax1AA/AA mouse optic stalk (OS) and grow slowly to arrive at the hypothalamus at a late stage. The RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas after failing to access the midline, resulting in reduced visual acuity and abnormal oculomotor responses. Overall, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the bilateral RGC axon projection in proper visuomotor responses.

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ER -

Visuomotor anomalies in achiasmatic mice expressing a transfer-defective Vax1 mutant

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