title: Injured adult retinal axons with Pten and Socs3 co-deletion reform active synapses with suprachiasmatic neurons.
abstract: Despite advances in promoting axonal regeneration after adult central nervous system injury, elicitation of a large number of lesion-passing axons reform active synaptic connections with natural target neurons remains limited. By deleting both Pten and Socs3 in retinal ganglion cells, we report that optic nerve axons after prechiasm lesion robustly reinnervate the hypothalamus, form new synapses with neurons in the suprachiasmatic nucleus (SCN), and re-integrate with the existing circuitry. Photic or electric stimulation of the retinal axons induces neuronal response in SCN. However both the innervation pattern and evoked responses are not completely restored by the regenerating axons, suggesting that combining with other strategies is necessary to overcome the defective rewiring. Our results support that boosting the intrinsic growth capacity in injured neurons promotes axonal reinnervation and rewiring.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Songshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: He
authors.affiliation: School of Life Sciences, Centre for Cell and Developmental Biology and State Key Laboratory of Agrobiotechnology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Tang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Kam Wing
authors.initials: KW
authors.lastname: Ho
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Annie
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Francis
authors.initials: F
authors.lastname: Wong
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Yung Hou
authors.initials: YH
authors.lastname: Wong
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
authors.affiliation: School of Life Sciences, Centre for Cell and Developmental Biology and State Key Laboratory of Agrobiotechnology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Jiang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Wing Ho
authors.initials: WH
authors.lastname: Yung
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: kailiu@ust.hk.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D007031:Hypothalamus / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000473:pathology / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D013493:Suprachiasmatic Nucleus / Q000473:pathology / Q000502:physiology*; D013569:Synapses / Q000473:pathology / Q000502:physiology*
chemical_list: C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Axon regeneration and rewiring; Intrinsic mechanisms; Pre-chiasm lesion; Retinal ganglion cells; Suprachiasmatic nucleus