PUBLICATION

Her9 controls the stemness properties of hindbrain boundary cells

Authors
Engel-Pizcueta, C., Hevia, C.F., Voltes, A., Livet, J., Pujades, C.
ID
ZDB-PUB-241204-10
Date
2024
Source
Development (Cambridge, England)   152(1): (Journal)
Registered Authors
Engel-Pizcueta, Carolyn, Hevia, Covadonga F., Pujades, Cristina
Keywords
her9, zebrabow2.0, Hindbrain boundaries, Multicolor clonal analysis, Neural progenitors, Zebrafish
MeSH Terms
  • Cyclin-Dependent Kinase Inhibitor p57/genetics
  • Cyclin-Dependent Kinase Inhibitor p57/metabolism
  • Signal Transduction
  • Animals
  • Neurogenesis*/physiology
  • Rhombencephalon*/cytology
  • Rhombencephalon*/embryology
  • Rhombencephalon*/metabolism
  • Gene Expression Regulation, Developmental
  • Cell Proliferation*
  • Ependymoglial Cells/cytology
  • Ependymoglial Cells/metabolism
  • Zebrafish*/embryology
  • Zebrafish*/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Receptors, Notch*/metabolism
PubMed
39628452 Full text @ Development
Abstract
The different spatiotemporal distribution of progenitor and neurogenic capacities permits that brain regions engage asynchronously in neurogenesis. In the hindbrain, rhombomere progenitor cells contribute to neurons during the first neurogenic phase, whereas boundary cells participate later. To analyze what maintains boundary cells as non-neurogenic progenitors, we addressed the role of Her9, a zebrafish Hes1-related protein. her9 expression is temporarily sustained in boundary cells independently of Notch at early embryonic stages, while they are non-neurogenic progenitors. Complementary functional approaches show that Her9 inhibits the onset of Notch-signaling and the neurogenic program, keeping boundary cells as progenitors. Multicolor clonal analysis combined with genetic perturbations reveal that Her9 expands boundary progenitors by promoting symmetric proliferative and preventing neurogenic cell divisions. Her9 also regulates the proliferation of boundary cells by inhibiting the cell cycle arrest gene cdkn1ca and interplaying with CyclinD1. Moreover, her9 is enriched in hindbrain radial glial cells at late embryonic stages independently of Notch. Altogether, Her9 maintains the stemness properties of hindbrain boundary progenitors and late radial glial cells, ensuing the different temporal distribution of neurogenic capacities within the hindbrain.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping