Ageing is a time-dependent functional decline affecting living organisms. Despite differences in lifespan, ageing is a universally inevitable gradual process leading to reduced fitness, increased susceptibility to pathologies and increased mortality rate. Along these lines, neural aging may be defined as a progressive loss of central nervous system function that promotes neurodegeneration and impairs neurogenesis. We envisage that genes controlling age-dependent processes act in continuity between development, adulthood, and aging. The starting point of our work is a list of brain age-regulated mRNAs that we have previously obtained by RNA-seq and validated by qPCR and in situ hybridization1. Among them, we are currently studying the function of znf367 gene, codifying a transcription factor. Functional studies suggested that this gene could be involved in the regulation of embryonic neurogenesis, both in Xenopus and Zebrafish embryos. In particular, znf367 emerged as a new player in primary neurogenesis regulating neuroblast cell-cycle progression2. As the znf367 mRNA is present in the zebrafish adult brain, especially in the medial subpallium and in the posterior zone of the dorsal telencephalic area, we hypothesized a znf367 role in the maintenance of neurogenic niches not only during embryonic development but also in adulthood. For this reason, we generated a zebrafish mutant line to knock-out znf367 for unveiling its role in adult neurogenesis. We used CRISPR/CAS9 technology to induce a mutation in the second exon encoding the first zinc finger domain of znf367. Preliminary results, obtained by molecular analysis on developing and adult brains, suggested a role of znf367 in controlling embryonic and adult neurogenesis affecting the neuroblast proliferation rate and the p53 expression. Understanding the genetic pathways and molecular mechanisms underlying embryonic and adult neurogenesis may represent the first step in defining interventions that could increase neurogenesis in the aged brain and that could prevent/delay neurodegenerative diseases.
FUNCTIONAL ANALYSIS OF THE AGE-REGULATED ZINC FINGER FACTOR ZNF367 IN EMBRYONIC AND ADULT NEUROGENESIS. Proceedings of the 66th Congress of the GEI-Italian Society of Development and Cell Biology (GEI-SIBSC) - Milan, 22 June 2021
Miriam De Sarlo;Valentina Naef;Chiara Gabellini;Pietro Vaninetti;Michela Ori
2021-01-01
Abstract
Ageing is a time-dependent functional decline affecting living organisms. Despite differences in lifespan, ageing is a universally inevitable gradual process leading to reduced fitness, increased susceptibility to pathologies and increased mortality rate. Along these lines, neural aging may be defined as a progressive loss of central nervous system function that promotes neurodegeneration and impairs neurogenesis. We envisage that genes controlling age-dependent processes act in continuity between development, adulthood, and aging. The starting point of our work is a list of brain age-regulated mRNAs that we have previously obtained by RNA-seq and validated by qPCR and in situ hybridization1. Among them, we are currently studying the function of znf367 gene, codifying a transcription factor. Functional studies suggested that this gene could be involved in the regulation of embryonic neurogenesis, both in Xenopus and Zebrafish embryos. In particular, znf367 emerged as a new player in primary neurogenesis regulating neuroblast cell-cycle progression2. As the znf367 mRNA is present in the zebrafish adult brain, especially in the medial subpallium and in the posterior zone of the dorsal telencephalic area, we hypothesized a znf367 role in the maintenance of neurogenic niches not only during embryonic development but also in adulthood. For this reason, we generated a zebrafish mutant line to knock-out znf367 for unveiling its role in adult neurogenesis. We used CRISPR/CAS9 technology to induce a mutation in the second exon encoding the first zinc finger domain of znf367. Preliminary results, obtained by molecular analysis on developing and adult brains, suggested a role of znf367 in controlling embryonic and adult neurogenesis affecting the neuroblast proliferation rate and the p53 expression. Understanding the genetic pathways and molecular mechanisms underlying embryonic and adult neurogenesis may represent the first step in defining interventions that could increase neurogenesis in the aged brain and that could prevent/delay neurodegenerative diseases.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
