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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 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.

SUBMITTER: Min KW

PROVIDER: S-EPMC9981622 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

Min Kwang Wook KW Kim Namsuk N Lee Jae Hoon JH Sung Younghoon Y Kim Museong M Lee Eun Jung EJ Kim Jong-Myeong JM Kim Jae-Hyun JH Lee Jaeyoung J Cho Wonjin W Yang Jee Myung JM Kim Nury N Kim Jaehoon J Lee C Justin CJ Park Young-Gyun YG Lee Seung-Hee SH Lee Han-Woong HW Kim Jin Woo JW

Experimental & molecular medicine 20230203 2

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<sup>AA/AA</sup> mice expressing the Vax1<sup>AA</sup> mutant, which is incapable of intercellular transfer. We found that R ...[more]

PMID: 36737666

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Project description:BackgroundDuring muscle regeneration, the chemokine CXCL12 (SDF-1) and the synthesis of some specific heparan sulfates (HS) have been shown to be critical. CXCL12 activity has been shown to be heavily influenced by its binding to extracellular glycosaminoglycans (GAG) by modulating its presentation to its receptors and by generating haptotactic gradients. Although CXCL12 has been implicated in several phases of tissue repair, the influence of GAG binding under HS influencing conditions such as acute tissue destruction remains understudied.MethodsTo investigate the role of the CXCL12/HS proteoglycan interactions in the pathophysiology of muscle regeneration, we performed two models of muscle injuries (notexin and freeze injury) in mutant CXCL12Gagtm/Gagtm mice, where the CXCL12 gene having been selectively mutated in critical binding sites of CXCL12 to interact with HS. Histological, cytometric, functional transcriptomic, and ultrastructure analysis focusing on the satellite cell behavior and the vessels were conducted on muscles before and after injuries. Unless specified, statistical analysis was performed with the Mann-Whitney test.ResultsWe showed that despite normal histology of the resting muscle and normal muscle stem cell behavior in the mutant mice, endothelial cells displayed an increase in the angiogenic response in resting muscle despite the downregulated transcriptomic changes induced by the CXCL12 mutation. The regenerative capacity of the CXCL12-mutated mice was only delayed after a notexin injury, but a severe damage by freeze injury revealed a persistent defect in the muscle regeneration of CXCL12 mutant mice associated with vascular defect and fibroadipose deposition with persistent immune cell infiltration.ConclusionThe present study shows that CXCL12 is crucial for proper muscle regeneration. We highlight that this homing molecule could play an important role in drastic muscle injuries and that the regeneration defect could be due to an impairment of angiogenesis, associated with a long-lasting fibro-adipogenic scar.

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

Publications

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

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