RRC ID |
33678
|
著者 |
Nakayama Y, Kikuta H, Kanai M, Yoshikawa K, Kawamura A, Kobayashi K, Wang Z, Khan A, Kawakami K, Yamasu K.
|
タイトル |
Gbx2 functions as a transcriptional repressor to regulate the specification and morphogenesis of the mid-hindbrain junction in a dosage- and stage-dependent manner.
|
ジャーナル |
Mech Dev
|
Abstract |
The Gbx subfamily of homeodomain transcription factors is involved in the positioning of the isthmus, which patterns the midbrain and cerebellum in vertebrates. To uncover the details of Gbx functions, we first examined the dose dependency of its effects on brain formation in zebrafish and found that high-dose gbx2 mRNA injection affected the entire forebrain and midbrain, whereas low-dose mRNA specifically disrupted the isthmic folding at the midbrain-hindbrain boundary (MHB) but only weakly affected the expression of genes involved in MHB specification. Thus, isthmus morphogenesis, and not its early specification, is highly sensitive to gbx2. Transient induction of heat-inducible gbx2 using transgenic fish showed that MHB specification is most sensitive to gbx2 at the end of epiboly and further suggested that otx2 is the direct target gene. These together demonstrate that gbx2 regulates both specification and morphogenesis of the MHB/isthmus region. Deletion analyses showed that both the N- and C-terminal regions contribute to the suppressive activity of Gbx2 against the anterior brain and that the N-terminal core region, including the Eh1 and proline-rich sequences, is required for this Gbx2 activity. Comparison of the effects of activated and repressive forms with wild-type Gbx2 suggested that Gbx2 functions as a transcriptional repressor, which was further evidenced by a luciferase assay in which gbx2 repressed the MHB enhancer of fgf8a in mouse P19 cells.
|
巻・号 |
130(11-12)
|
ページ |
532-52
|
公開日 |
2013-1-1
|
DOI |
10.1016/j.mod.2013.07.004
|
PII |
S0925-4773(13)00059-2
|
PMID |
23933069
|
MeSH |
Animals
Animals, Genetically Modified
Body Patterning / genetics*
Cell Line, Tumor
Embryo, Nonmammalian
Fibroblast Growth Factor 8 / genetics
Fibroblast Growth Factor 8 / metabolism
Gene Dosage
Gene Expression Regulation, Developmental
Genes, Reporter
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Injections, Intraventricular
Luciferases / genetics
Luciferases / metabolism
Mesencephalon / anatomy & histology
Mesencephalon / embryology
Mesencephalon / metabolism*
Mice
Prosencephalon / anatomy & histology
Prosencephalon / embryology
Prosencephalon / metabolism*
Protein Structure, Tertiary
RNA, Messenger / administration & dosage
RNA, Messenger / genetics*
RNA, Messenger / metabolism
Rhombencephalon / anatomy & histology
Rhombencephalon / embryology
Rhombencephalon / metabolism*
Signal Transduction
Transcription, Genetic
Zebrafish / anatomy & histology
Zebrafish / embryology
Zebrafish / genetics*
Zebrafish / metabolism
Zebrafish Proteins / genetics*
Zebrafish Proteins / metabolism
|
IF |
2.126
|
引用数 |
11
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
|
リソース情報 |
ゼブラフィッシュ |
sud12(Tg(hsp70l:gbx2)) |