Abstract
Global population aging is one of the major social and economic challenges of contemporary society. During aging the progressive decline in physiological functions has serious consequences for all organs including brain. The age-related incidence of neurodegenerative diseases coincides with the sharp decline of the amount and functionality of adult neural stem cells. Recently, we identified a short list of brain age-regulated genes by means of next-generation sequencing. Among them znf367 codes for a transcription factor that represents a central node in gene co-regulation networks during aging, but whose function in the central nervous system (CNS), is completely unknown. As proof of concept, we analysed the role of znf367 during Xenopus laevis neurogenesis. By means of a gene loss of function approach limited to the CNS, we suggested that znf367 might act as a key controller of the neuroblast cell cycle, particularly in the progression of mitosis and spindle checkpoint. A candidate gene approach based on a weighted-gene co-expression network analysis, revealed fancd2 and ska3 as possible targets of znf367. The age-related decline of znf367 correlated well with its role during embryonic neurogenesis, opening new lines of investigation also in adult neurogenesis to improved maintenance and even repair of neuronal function.
Highlights
The age-related incidence of many brain diseases coincides with a reduced adult neurogenic potential
We show that znf[367] is expressed in the developing Central Nervous System (CNS) in Xenopus and it could have a key role in primary neurogenesis, regulating the neuroblast progression of mitosis
Znf[367] is widely expressed in the central nervous system, in the eye, in the otic vesicle and in the neural crest cells (NCC) migrated in the branchial pouches (Fig. 2D)
Summary
The age-related incidence of many brain diseases coincides with a reduced adult neurogenic potential. In the Supplementary materials (Table S7), the authors compared the trascriptome of young (3–4 month-old) quiescent neural stem cells to the one obtained from old (19–22 month-old) quiescent neural stem cells and znf[367] (zfp367) emerged among the genes significantly down regulated in the old mice[12] Despite this data confirmed that, even in mammals, znf[367] is an age-regulated gene in the adult brain, its function in the CNS remained unknown. In Xenopus, it is possible to microinject mRNAs or morpholino oligos in just one side of the early cleaving embryo and compare, in each embryo, the manipulated side of the embryo with its wild-type counterpart that represents a perfect internal control This unique vertebrate model provide the possibility, to rapidly perform gene loss of function experiments in a tissue specific manner thanks to the well-defined fate map of each blastomere of the early cleaving embryo. These finding, together with the znf[367] gene expression decline observed during CNS aging, lay the groundwork for future studies aimed to unveil znf[367] role in adult neurogenesis and CNS aging
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
