Function and mechanism of CNTF/LIF signaling in retinogenesis.

Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) exhibit multiple biological effects in the developing vertebrate retina. CNTF/LIF inhibits rod photoreceptor, and promotes bipolar cells and Muller glia differentiation. In addition, CNTF/LIF has been shown to have proliferative and apoptotic effects. Moreover, LIF also inhibits retinal vascular development. CNTF/LIF signaling components CNTFRalpha, LIFRbeta, gp130, and a number of STAT proteins are expressed in the retina. CNTF/LIF activates Jak-STAT, ERK, and Notch pathways during retinal development. Perturbation of CNTF induced signal transduction reveals that different combinations of CNTF/LIF signaling pathways regulate differentiation of retinal neurons and glia. Gene expression studies show that CNTF/LIF affects retinogenesis by regulating various genes involved in transcription, signal transduction, protein modification, apoptosis, protein localization, and cell ion homeostasis. Most past studies have deployed ectopic expression or addition of exogenous CNTF/LIF, thus further ana-lysis of mice with conditional mutations in CNTF/LIF signaling components will allow better understanding of in-vivo functions of CNTF/LIF associated signaling events in retinogenesis.