| RRC ID |
60013
|
| 著者 |
Turner KJ, Hoyle J, Valdivia LE, Cerveny KL, Hart W, Mangoli M, Geisler R, Rees M, Houart C, Poole RJ, Wilson SW, Gestri G.
|
| タイトル |
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.
|
| ジャーナル |
PLoS One
|
| Abstract |
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 expression of modules of developmental regulatory genes that characterise, or promote transitions in, cell state and require the correct function of Slbp-dependent histone and chromatin regulatory genes.
|
| 巻・号 |
14(1)
|
| ページ |
e0211073
|
| 公開日 |
2019-1-1
|
| DOI |
10.1371/journal.pone.0211073
|
| PII |
PONE-D-19-00337
|
| PMID |
30695021
|
| PMC |
PMC6350959
|
| MeSH |
Animals
Animals, Genetically Modified* / embryology
Animals, Genetically Modified* / genetics
Axon Guidance / genetics*
Cell Differentiation*
Cell Proliferation*
Coloboma* / embryology
Coloboma* / genetics
Coloboma* / pathology
Histones / genetics
Histones / metabolism
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Retinal Diseases* / embryology
Retinal Diseases* / genetics
Retinal Diseases* / pathology
Zebrafish* / embryology
Zebrafish* / genetics
Zebrafish Proteins / deficiency*
|
| IF |
2.776
|
| 引用数 |
3
|
| リソース情報 |
| ゼブラフィッシュ |
Tg(EF1α:mAG-zGem(1/100))rw0410h
Tg(EF1α:mKO2-zCdt1(1/190))rw0405b |
