The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation

Sara Mancinelli, Michela Vitiello, Maria Donnini, Francesca Mantile, Giuseppe Palma, Antonio Luciano, Claudio Arra, Laura Cerchia, Giovanna Lucia Liguori, Monica Fedele

Research output: Contribution to journalArticlepeer-review

Abstract

Proper regulation of neurogenesis, the process by which new neurons are generated from neural stem and progenitor cells (NS/PCs), is essential for embryonic brain development and adult brain function. The transcription regulator Patz1 is ubiquitously expressed in early mouse embryos and has a key role in embryonic stem cell maintenance. At later stages, the detection of Patz1 expression mainly in the developing brain suggests a specific involvement of Patz1 in neurogenesis. To address this point, we first got insights in Patz1 expression profile in different brain territories at both embryonic and postnatal stages, evidencing a general decreasing trend with respect to time. Then, we performed in vivo and ex vivo analysis of Patz1-knockout mice, focusing on the ventricular and subventricular zone, where we confirmed Patz1 enrichment through the analysis of public RNA-seq datasets. Both embryos and adults showed a significant reduction in the number of Patz1-null NS/PCs, as well as of their self-renewal capability, compared to controls. Consistently, molecular analysis revealed the downregulation of stemness markers in NS/PCs derived from Patz1-null mice. Overall, these data demonstrate the requirement of Patz1 for NS/PC maintenance and proliferation, suggesting new roles for this key transcription factor specifically in brain development and plasticity, with possible implications for neurodegenerative disorders and glial brain tumors.

Original languageEnglish
Article number657149
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
Publication statusPublished - Apr 7 2021

Keywords

  • knockout mice
  • neural stem cells
  • neurogenesis
  • neurosphere assay
  • PATZ1
  • subventricular zone

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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