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Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits

Turner, Kate; Hoyle, Jaqueline; Valdivia, Leonardo E.; Cerveny, Kara; Hart, Wendy; Mangoli, Maryam; Geisler, Robert; Rees, Michele; Houart, Corinne; Poole, Richard J.; Wilson, Steve W.; Gestri, Gaia

Abstract (englisch):
Through forward genetic screening for mutations affecting visual system development, we identified prominent coloboma and cell-autonomous retinal neuron differentiation, lamination and retinal axon projection defects in eisspalte (ele) mutant zebrafish. Additional axonal deficits were present, most notably at midline axon commissures. Genetic mapping and cloning of the ele mutation showed that the affected gene is slbp, which encodes a conserved RNA stem-loop binding protein involved in replication dependent histone mRNA metabolism. Cells throughout the central nervous system remained in the cell cycle in ele mutant embryos at stages when, and locations where, post-mitotic cells have differentiated in wild-type siblings. Indeed, RNAseq analysis showed down-regulation of many genes associated with neuronal differentiation. This was coincident with changes in the levels and spatial localisation of expression of various genes implicated, for instance, in axon guidance, that likely underlie specific ele phenotypes. These results suggest that many of the cell and tissue specific phenotypes in ele mutant embryos are secondary to altered e ... mehr

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Volltext §
DOI: 10.5445/IR/1000089053
Veröffentlicht am 14.01.2019
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Sonstiges
Jahr 2018
Sprache Englisch
Identifikator urn:nbn:de:swb:90-890535
KITopen-ID: 1000089053
HGF-Programm 47.01.01 (POF III, LK 01)
Bemerkung zur Veröffentlichung bioRxiv.org
Vorab online veröffentlicht am 06.11.2018
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