PUBLICATION
Transcriptional repressor foxl1 regulates central nervous system development by suppressing shh expression in zebra fish
- Authors
- Nakada, C., Satoh, S., Tabata, Y., Arai, K., and Watanabe, S.
- ID
- ZDB-PUB-061222-15
- Date
- 2006
- Source
- Molecular and cellular biology 26(19): 7246-7257 (Journal)
- Registered Authors
- Watanabe, Sumiko
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Biomarkers
- Brain/cytology
- Brain/embryology*
- Brain/metabolism
- Cells, Cultured
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Fibroblasts/metabolism
- Forkhead Transcription Factors/chemistry
- Forkhead Transcription Factors/isolation & purification
- Forkhead Transcription Factors/metabolism*
- Gastrula/metabolism
- Gene Expression Regulation, Developmental*
- Hedgehog Proteins
- Mice
- Molecular Sequence Data
- NIH 3T3 Cells
- Oligonucleotides, Antisense/metabolism
- PC12 Cells
- Promoter Regions, Genetic/genetics
- Protein Binding
- Protein Structure, Tertiary
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Rats
- Repressor Proteins/chemistry
- Repressor Proteins/isolation & purification
- Repressor Proteins/metabolism*
- Trans-Activators/genetics
- Trans-Activators/metabolism*
- Transcription, Genetic*
- Zebrafish/embryology
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/isolation & purification
- Zebrafish Proteins/metabolism*
- PubMed
- 16980626 Full text @ Mol. Cell. Biol.
Citation
Nakada, C., Satoh, S., Tabata, Y., Arai, K., and Watanabe, S. (2006) Transcriptional repressor foxl1 regulates central nervous system development by suppressing shh expression in zebra fish. Molecular and cellular biology. 26(19):7246-7257.
Abstract
We identified zebra fish forkhead transcription factor l1 (zfoxl1) as a gene strongly expressed in neural tissues such as midbrain, hindbrain, and the otic vesicle at the early embryonic stage. Loss of the function of zfoxl1 effected by morpholino antisense oligonucleotide resulted in defects in midbrain and eye development, and in that of formation of the pectoral fins. Interestingly, ectopic expression of shh in the midbrain and elevated pax2a expression in the optic stalk were observed in foxl1 MO-injected embryos. In contrast, expression of pax6a, which is negatively regulated by shh, was suppressed in the thalamus and pretectum regions, supporting the idea of augmentation of the shh signaling pathway by suppression of foxl1. Expression of zfoxl1-EnR (repressing) rather than zfoxl1-VP16 (activating) resulted in a phenotype similar to that induced by foxl1-mRNA, suggesting that foxl1 may act as a transcriptional repressor of shh in zebra fish embryos. Supporting this notion, foxl1 suppressed isolated 2.7-kb shh promoter activity in PC12 cells, and the minimal region of foxl1 required for its transcriptional repressor activity showed strong homology with the groucho binding motif, which is found in genes encoding various homeodomain proteins. In view of all of our data taken together, we propose zfoxl1 to be a novel regulator of neural development that acts by suppressing shh expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping