2. Academic Validation
  3. DNA template strand segregation in developing zebrafish

DNA template strand segregation in developing zebrafish

  • Cell Chem Biol. 2021 Nov 18;28(11):1638-1647.e4. doi: 10.1016/j.chembiol.2021.09.001.
Stella M K Glasauer 1,  Therese Triemer 2,  Anne B Neef 2,  Stephan C F Neuhauss 3,  Nathan W Luedtke 4
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara CA 93106, USA.
  • 2 Department of Chemistry, University of Zurich, 8057 Zurich, Switzerland.
  • 3 Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland. Electronic address: stephan.neuhauss@mls.uzh.ch.
  • 4 Department of Chemistry, University of Zurich, 8057 Zurich, Switzerland; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada; Department of Chemistry, McGill University, Montreal, QC H3A 0B8, Canada. Electronic address: nathan.luedtke@mcgill.ca.
PMID: 34592171 DOI: 10.1016/j.chembiol.2021.09.001
Abstract

Asymmetric inheritance of sister chromatids has long been predicted to be linked to discordant fates of daughter cells and even hypothesized to minimize accumulation of mutations in stem cells. Here, we use (2'S)-2'-deoxy-2'-fluoro-5-ethynyluridine (F-ara-EdU), bromodeoxyuridine (BrdU), and light sheet microscopy to track embryonic DNA in whole zebrafish. Larval development results in rapid depletion of older DNA template strands from stem cell niches in the retina, brain, and intestine. Prolonged label retention occurs in quiescent progenitors that resume replication in later development. High-resolution microscopy reveals no evidence of asymmetric template strand segregation in >100 daughter cell pairs, making it improbable that asymmetric DNA segregation prevents mutational burden according to the immortal strand hypothesis in developing zebrafish.

Keywords

DNA metabolic labeling; azide-alkyne "click" cycloaddition; cell division; developmental biology; eye development; fluorescence microscopy; stem cells.

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