The Pax-6 gene encodes a transcriptional master regulator involved in the d
evelopment of the eye. The quail Pax-6 gene is expressed in the neuroretina
from two promoters, P0 and P1, P0 being activated at the onset of neuronal
differentiation.. In this paper we have identified two regions in the quai
l Pax-6 gene 5' flanking sequences, located 6 and 2.5 kbp upstream from the
P0 promoter that, like the previously characterised intragenic enhancer (E
P enhancer), function as neuroretina-specific enhancers whose activity is r
estricted to the PO promoter. Moreover, the activity of these 5' enhancers
in embryonic neuroretina cells is weaker at day 5 than at day 7, like the E
P enhancer, and parallels the level of expression of P0-initiated mRNAs. Fo
otprinting experiments show that neuroretina-specific factors bind to these
5' enhancer elements. In addition we show that these quail Pax-6 enhancer
elements, as well as the P0 promoter, are structurally and functionally con
served in humans. These results strongly suggest that these enhancer elemen
ts may contribute to the neuroretina-specific transcriptional regulation of
the Pax-6 gene in vivo. Thus the complex regulation of the quail Pax-6 gen
e is also conserved in humans.