MAMMALIAN HAIRY AND ENHANCER OF SPLIT HOMOLOG-1 REGULATES DIFFERENTIATION OF RETINAL NEURONS AND IS ESSENTIAL FOR EYE MORPHOGENESIS

Mammalian hairy and Enhancer of split homolog 1 (HES1), a basic helix- loop-helix factor gene, is expressed in retinal progenitor cells, and its expression decreases as differentiation proceeds. Retinal progenit or cells infected with HES1-transducing retrovirus did not differentia te into mature retinal cells, suggesting that persistent expression of HES1 blocks retinal development. In contrast, in the retina of HES1-n ull mutant mice, differentiation was accelerated, and rod and horizont al cells appeared prematurely and formed abnormal rosette-like structu res. Lens and cornea development was also severely disturbed. Furtherm ore, in the mutant retina, bipolar cells extensively died and finally disappeared. These studies provide evidence that HES1 regulates differ entiation of retinal neurons and is essential for eye morphogenesis.