A Notch-mediated, temporal asymmetry in BMP pathway activation promotes photoreceptor subtype diversification

PLoS Biol. 2019 Jan 31;17(1):e2006250. doi: 10.1371/journal.pbio.2006250. eCollection 2019 Jan.

Abstract

Neural progenitors produce neurons whose identities can vary as a function of the time that specification occurs. Here, we describe the heterochronic specification of two photoreceptor (PhR) subtypes in the zebrafish pineal gland. We find that accelerating PhR specification by impairing Notch signaling favors the early fate at the expense of the later fate. Using in vivo lineage tracing, we show that most pineal PhRs are born from a fate-restricted progenitor. Furthermore, sister cells derived from the division of PhR-restricted progenitors activate the bone morphogenetic protein (BMP) signaling pathway at different times after division, and this heterochrony requires Notch activity. Finally, we demonstrate that PhR identity is established as a function of when the BMP pathway is activated. We propose a novel model in which division of a progenitor with restricted potential generates sister cells with distinct identities via a temporal asymmetry in the activation of a signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Lineage
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Neurons / metabolism
  • Photoreceptor Cells, Vertebrate / physiology*
  • Pineal Gland / embryology*
  • Pineal Gland / metabolism
  • Pineal Gland / physiology
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • Time Factors
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Receptors, Notch
  • Zebrafish Proteins

Grant support

CNRS www.cnrs.fr. To PB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. INSERM www.inserm.fr. To PB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Université Toulouse III www.univ-tlse3.fr. To PB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. FRM www.frm.orf (grant number DEQ20131029166). To PB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. FRC www.frcneurodon.org. To PB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ministère de la recherche www.enseignementsup-recherche.gouv.fr. To PB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.