Lmx1b is essential for survival of periocular mesenchymal cells and influences Fgf-mediated retinal patterning in zebrafish. Dev Biol 2009 Aug 15;332(2):287-98
Date
06/09/2009Pubmed ID
19500562Pubmed Central ID
PMC2716413DOI
10.1016/j.ydbio.2009.05.577Scopus ID
2-s2.0-67650960647 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
To gain insight into the mechanisms of Lmx1b function during ocular morphogenesis, we have studied the roles of lmx1b.1 and lmx1b.2 during zebrafish eye development. In situ hybridization and characterization of transgenic lines in which GFP is expressed under lmx1b.1 regulatory sequence show that these genes are expressed in periocular tissues and in a pattern conserved with other vertebrates. Anti-sense morpholinos against lmx1b.1 and lmx1b.2 result in defective migration of periocular mesenchymal cells around the eye and lead to apoptosis of these cells. These defects in the periocular mesenchyme are correlated with a failure in fusion of the choroid fissure or in some instances, more severe ventral optic cup morphogenesis phenotypes. Indeed, by blocking the death of the periocular mesenchyme in Lmx1b morphants, optic vesicle morphogenesis is largely restored. Within the retina of lmx1b morphants, Fgf activity is transiently up-regulated and these morphants show defective naso-temporal patterning. Epistasis experiments indicate that the increase in Fgf activity is partially responsible for the ocular anomalies caused by loss of Lmx1b function. Overall, we propose zebrafish lmx1b.1 and lmx1b.2 promote the survival of periocular mesenchymal cells that influence multiple signaling events required for proper ocular development.
Author List
McMahon C, Gestri G, Wilson SW, Link BAAuthor
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Genetically Modified
Fibroblast Growth Factors
Forkhead Transcription Factors
Gene Expression Regulation, Developmental
Homeodomain Proteins
In Situ Hybridization
LIM-Homeodomain Proteins
Mesoderm
Molecular Sequence Data
Morphogenesis
Oligonucleotides, Antisense
Recombinant Fusion Proteins
Retina
Signal Transduction
Transcription Factors
Zebrafish
Zebrafish Proteins
