| Midbrain-hindbrain boundary patterning and morphogenesis are regulated by diverse grainy head-like 2-dependent pathways. | |
| | |
MedLine Citation:
|
PMID: 22223680 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
The isthmic organiser located at the midbrain-hindbrain boundary (MHB) is the crucial developmental signalling centre responsible for patterning mesencephalic and metencephalic regions of the vertebrate brain. Formation and maintenance of the MHB is characterised by a hierarchical program of gene expression initiated by fibroblast growth factor 8 (Fgf8), coupled with cellular morphogenesis, culminating in the formation of the tectal-isthmo-cerebellar structures. Here, we show in zebrafish that one orthologue of the transcription factor grainy head-like 2 (Grhl2), zebrafish grhl2b plays a central role in both MHB maintenance and folding by regulating two distinct, non-linear pathways. Loss of grhl2b expression induces neural apoptosis and extinction of MHB markers, which are rescued by re-expression of engrailed 2a (eng2a), an evolutionarily conserved target of the Grhl family. Co-injection of sub-phenotypic doses of grhl2b and eng2a morpholinos reproduces the apoptosis and MHB marker loss, but fails to substantially disrupt formation of the isthmic constriction. By contrast, a novel direct grhl2b target, spec1, identified by phylogenetic analysis and confirmed by ChIP, functionally cooperates with grhl2b to induce MHB morphogenesis, but plays no role in apoptosis or maintenance of MHB markers. Collectively, these data show that MHB maintenance and morphogenesis are dissociable events regulated by grhl2b through diverse transcriptional targets. |
| | |
Authors:
|
Sebastian Dworkin; Charbel Darido; Smitha R Georgy; Tomasz Wilanowski; Seema Srivastava; Felix Ellett; Luke Pase; Yanchao Han; Anming Meng; Joan K Heath; Graham J Lieschke; Stephen M Jane |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Development (Cambridge, England) Volume: 139 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2012 Feb |
Date Detail:
|
Created Date: 2012-01-06 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
|
Languages: eng Pagination: 525-36 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Monash University Central Clinical School, Prahran VIC 3181, Australia. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Drosophila aPKC is required for mitotic spindle orientation during symmetric division of epithelial ...
Next Document: CycA is involved in the control of endoreplication dynamics in the Drosophila bristle lineage.