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

• 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
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2018.02.006

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.