Inhibition of protein tyrosine kinase activity disrupts early retinal development.
In the present study, we have investigated the role of tyrosine kinase activity during early retinal development in Xenopus laevis. The protein tyrosine kinase (PTK) inhibitors lavendustin A and genistein were used to determine the possible role of tyrosine kinase activity during retinal development in vivo and in vitro. Application of the inhibitors to early embryonic retina disrupted the pattern of lamination in the developing retina. The plexiform layers were severely disorganized or were no longer apparent, and photoreceptor morphogenesis was disrupted. Immunocytochemical analysis verified the presence of focal adhesions in dissociated retinal neuroepithelial cells isolated from St 25 embryos. Application of the PTK inhibitors blocked focal adhesion assembly in these primary cultured cells. To further investigate the regulation of focal adhesions by PTK activity, we examined the effect of lavendustin A on cultured XR1 glial cells. Lavendustin A produced a dose-dependent decrease in the proportion of XR1 cells displaying focal adhesions. Taken together, these results suggest that tyrosine kinase activity is essential for regulating neuroepithelial cell adhesion, migration and morphogenesis during retinal development. Furthermore, the disruption of retinal development may, in part, be due to the inhibition of integrin-mediated signaling.
Li
Ming
M
Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Babenko
Nataliya A
NA
Sakaguchi
Donald S
DS
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012160:Retina / Q000196:embryology* / Q000201:enzymology; D014982:Xenopus laevis / Q000196:embryology
D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases