Document Detail


Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary.
MedLine Citation:
PMID:  21266408     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vertebrates, the common expression border of two homeobox genes, Otx2 and Gbx2, demarcates the prospective midbrain-hindbrain border (MHB) in the neural plate at the end of gastrulation. The presence of a compartment boundary at the MHB has been demonstrated, but the mechanism and timing of its formation remain unclear. We show by genetic inducible fate mapping using a Gbx2(CreER) knock-in mouse line that descendants of Gbx2(+) cells as early as embryonic day (E) 7.5 do not cross the MHB. Without Gbx2, hindbrain-born cells abnormally populate the entire midbrain, demonstrating that Gbx2 is essential for specifying hindbrain fate. Gbx2(+) and Otx2(+) cells segregate from each other, suggesting that mutually exclusive expression of Otx2 and Gbx2 in midbrain and hindbrain progenitors is responsible for cell sorting in establishing the MHB. The MHB organizer gene Fgf8, which is expressed as a sharp transverse band immediately posterior to the lineage boundary at the MHB, is crucial in maintaining the lineage-restricted boundary after E7.5. Partial deletion of Fgf8 disrupts MHB lineage separation. Activation of FGF pathways has a cell-autonomous effect on cell sorting in midbrain progenitors. Therefore, Fgf8 from the MHB may signal the nearby mesencephalic cells to impart distinct cell surface characteristics or induce local cell-cell signaling, which consequently prevents cell movements across the MHB. Our findings reveal the distinct function of Gbx2 and Fgf8 in a stepwise process in the development of the compartment boundary at the MHB and that Fgf8, in addition to its organizer function, plays a crucial role in maintaining the lineage boundary at the MHB by restricting cell movement.
Authors:
N Abimbola Sunmonu; Kairong Li; Qiuxia Guo; James Y H Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-03-02     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  725-34     Citation Subset:  IM    
Affiliation:
Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Lineage
Fibroblast Growth Factor 8 / genetics,  metabolism*
Gene Deletion
Gene Expression Regulation, Developmental
Homeodomain Proteins / genetics,  metabolism*
Mesencephalon / cytology,  embryology*,  metabolism*
Mice
Mice, Transgenic
Rhombencephalon / cytology,  embryology*,  metabolism*
Signal Transduction
Grant Support
ID/Acronym/Agency:
1R01HD050474/HD/NICHD NIH HHS; R01 HD050474/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Fgf8 protein, mouse; 0/Gbx2 protein, mouse; 0/Homeodomain Proteins; 148997-75-5/Fibroblast Growth Factor 8
Comments/Corrections

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