Fibrillarin is essential for S-phase progression and neuronal differentiation in zebrafish dorsal midbrain and retina

Fibrillarin (Fbl) is a highly conserved protein that plays an essential role in ribosome biogenesis and more particularly in the methylation of ribosomal RNAs and rDNA histones. In cellular models, FBL was shown to play an important role in tumorigenesis and stem cell differentiation. We used the ze...

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Bibliographic Details
Published in:Developmental biology 2018-05, Vol.437 (1), p.1-16
Main Authors: Bouffard, Stéphanie, Dambroise, Emilie, Brombin, Alessandro, Lempereur, Sylvain, Hatin, Isabelle, Simion, Matthieu, Corre, Raphaël, Bourrat, Franck, Joly, Jean-Stéphane, Jamen, Françoise
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell cycle regulation
Cell Differentiation
Chromosomal Proteins, Non-Histone
Cognitive Sciences
Danio rerio
Differentiation
Larva
Life Sciences
Mesencephalon
Morphogenesis
Neural progenitors
Neurobiology
Neurogenesis
Neurons and Cognition
Optic tectum
Psychology and behavior
Retina
Ribosome biogenesis
RNA, Ribosomal
S Phase
Zebrafish
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Summary:Fibrillarin (Fbl) is a highly conserved protein that plays an essential role in ribosome biogenesis and more particularly in the methylation of ribosomal RNAs and rDNA histones. In cellular models, FBL was shown to play an important role in tumorigenesis and stem cell differentiation. We used the zebrafish as an in vivo model to study Fbl function during embryonic development. We show here that the optic tectum and the eye are severely affected by Fbl depletion whereas ventral regions of the brain are less impacted. The morphogenesis defects are associated with impaired neural differentiation and massive apoptosis. Polysome gradient experiments show that fbl mutant larvae display defects in ribosome biogenesis and activity. Strikingly, flow cytometry analyses revealed different S-phase profiles between wild-type and mutant cells, suggesting a defect in S-phase progression. •Zebrafish mutant line was used to study the role of nucleolar Fibrillarin.•Fibrillarin is essential for correct ribosome biogenesis and activity.•Dorsal but not ventral midbrain display severe developmental defects.•In mutant, no neuronal differentiation occur in retina and optic tectum.•Fibrillarin depletion alters S-phase progression.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2018.02.006