PTP-Meg2 - A New Functional Player During Early Retinogenesis?

Abstract

Purpose: : The developing retina serves as one of the best characterized model systems to investigate neuronal development. In this context, the phosphorylation and dephosphorylation of proteins on tyrosine residues represents a key mechanism for the control of numerous processes, including cell proliferation, differentiation, migration and maturation. In order to investigate the potential functional role of the protein tyrosine phosphatase (PTP) Meg2 during retinal development, we performed studies in PTP-Meg2 knockout (KO) mice (Wang et al., 2005).

Methods: : Histological studies, including immunohistochemistry and in situ-hybridization, as well as molecular biological techniques such as RT-PCR and microarray analyses were performed to investigate retinal development of PTP-Meg2 KO animals.

Results: : In order to elucidate the functional role of PTP-Meg2 during retinogenesis, we analyzed PTP-Meg2 deficient animals. We demonstrate that PTP-Meg2 deficient mice exhibit a "small-eye phenotype", a hypocellular retina and a reduced proliferation capacity. In addition, in the PTP-Meg2 deficient retina amacrine cell differentiation was inhibited. In contrast, we present evidence that progenitors of PTP-Meg2 KO animals adopt bipolar cell properties. Most interestingly, based on microarray analysis using retinae of newborn PTP-Meg2 KO and wildtype (WT) control littermates, we verified a dysregulation of several genes highly associated with early synaptogenesis.

Conclusions: : In conclusion, our results suggest that PTP-Meg2 plays different roles, at defined time points of retinal development. Our data provide an important basis for future studies regarding the functional importance of PTP-Meg2 during retinal and CNS development.

Keywords: retinal development • differentiation • gene microarray