Phenotypic analyses of mouse embryos with ubiquitous expression of Oct4: effects on mid-hindbrain patterning and gene expression.
Oct4 is a transcription factor that has been associated with pluripotency and fate determination in the initial cell lineages of mammals. On the other hand, Pou2, the ortholog of Oct4 in zebrafish, serves additional later functions during brain development acting as a differentiation switch. In mice, Oct4 is expressed throughout the neural plate of embryos until embryonic day (E) 8.0. In this study, we produced transgenic mouse embryos that ubiquitously express Oct4 and analyzed the consequences during development. We show that, at E8.0, a higher dosage of Oct4 in the neuroectoderm is sufficient to transiently alter mid-hindbrain patterning and produced a strong up-regulation of Pax2, indicating that Oct4 can regulate this gene in vivo. After E9.5, ectopic Oct4 in this region produced cell death and affected the development of the forebrain, suggesting that, at these later stages, Oct4 down-regulation is necessary for normal development to proceed. The phenotype of the transgenic embryos was also accompanied with an increase of Fgf8 expression in several of its endogenous domains, suggesting the possibility that Oct4 can participate in the regulation of expression of this ligand. Our observations support the hypothesis that Oct4, like zebrafish Pou2, has a conserved function during early brain patterning in mouse.
Ramos-Mejía
Verónica
V
Departamento de Fisiología Molecular y Genética del Desarrollo, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Escalante-Alcalde
Diana
D
Kunath
Tilo
T
Ramírez
Laura
L
Gertsenstein
Marina
M
Nagy
Andras
A
Lomelí
Hilda
H
D000818:Animals; D015153:Blotting, Western; D019521:Body Patterning; D001921:Brain / Q000196:embryology*; D016923:Cell Death; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015536:Down-Regulation; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008957:Models, Genetic; D008969:Molecular Sequence Data; D050814:Octamer Transcription Factor-3; D051762:PAX2 Transcription Factor; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014158:Transcription, Genetic; D019076:Transgenes; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; D008024:Ligands; D050814:Octamer Transcription Factor-3; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors