Temporal requirement of the protein tyrosine phosphatase Shp2 in establishing the neuronal fate in early retinal development.
FGF signaling is critical in the development of the vertebrate retina, which differentiates in a wave-like pattern similar to that found in the Drosophila eye. In this study, we investigated the mechanism of FGF signaling in vertebrate eye development by identifying Shp2, a protein tyrosine phosphatase, as a novel factor in orchestrating retinal morphogenesis. Using a series of Shp2 conditional mutants, we have shown that Shp2 is specifically required for the initiation of retinal neurogenesis but not for the maintenance of the retinal differentiation program. By mosaic deletion of Shp2, we further demonstrated that Shp2 ablation did not prevent the spreading of the retinal differentiation wave. Shp2 instead controls the patterning of the optic vesicle by regulating the retinal progenitor factors and cell proliferation. In ex vivo culture models and genetic rescue experiments, we showed that Shp2 acts downstream to FGF signaling in retinal development and that it can be functionally substituted by activated Ras signaling. Together, these results demonstrate that Shp2 mediates FGF-Ras signaling to control retinal progenitor cell fate.
Cai
Zhigang
Z
Department of Medical and Molecular Genetics, Stark Neuroscience Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Feng
Gen-Sheng
GS
Zhang
Xin
X
D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology; D017353:Gene Deletion; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009924:Organ Culture Techniques; D019899:Paracrine Communication / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D013997:Time Factors
D005346:Fibroblast Growth Factors; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse