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Han-Pang Hsu, Bor-Sen Chen, Chuan-Chin Chiao; Characterization of the Genetic Regulatory Network Responsible for the Developmental Loss of Axon Regeneration Ability. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4560.
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© ARVO (1962-2015); The Authors (2016-present)
Mammalian retinal ganglion cells (RGCs) lose their ability to regenerate axons during development. While several intrinsic and extrinsic axon growth regulators of RGCs during their development have been identified, the coordination among these regulators, which is essential for their contributions to the axon regeneration ability of RGCs, remains largely unknown.
In this work, we used the systems biology approach to construct the genome-wide integrated genetic-regulatory and protein-protein-interaction network of rat RGCs during development, based on the microarray data from Goldberg’s lab (Wang et al., 2007). We first constructed the candidate network by big data mining, and then constructed the real network of RGCs during development via their microarray data by system identification and model order selection methods. We used the principal network projection to obtain the core network key to the development of RGCs, and identified the cellular pathways that interact with the axon growth regulators in the core network.
We found that the previously identified axon growth regulators are involved in the core biological network of RGCs during development, and the involvement of the individual intrinsic and extrinsic regulators changes over time as the RGCs mature. There is a wide range of dependence among different axon growth regulators as well as between the axon growth regulators and the regulators of other cellular responses. In addition, the coordination among these regulators is mediated by a specific group of transcription factors. During development, both the dependence of the axon growth regulators on each other and on other cellular pathways, and the transcription factors that coordinate the interaction, undergo significant changes, which marks the transition in the loss of axon regeneration ability of RGCs.
Based on the characterization of the genetic regulatory network in developing rat retinas, we provided the genome-wide molecular mechanisms that mediate the loss of axon regeneration ability of RGCs during development. From these results, we proposed a group of network-based biomarkers for axon growth as the potential targets of modulation that may promote the axon regeneration ability of adult RGCs after injury.
This is a 2020 ARVO Annual Meeting abstract.
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