SENSITIVITY OF PRONEURAL GENES TO LATERAL INHIBITION AFFECTS THE PATTERN OF PRIMARY NEURONS IN XENOPUS EMBRYOS

We have compared the roles of XASH-3 and NeuroD, two basic helix-loop- helix transcription factors, in the formation of primary neurons in ea rly Xenopus embryos. When ectopically expressed in Xenopus embryos, XA SH-3 and NeuroD induce ectopic primary neurons in very different spati al patterns. We show that the pattern of primary neurons induced by XA SH-3 and NeuroD can be accounted for by a difference in their sensitiv ity to inhibitory interactions mediated by the neurogenic genes, X-Del ta-1 and X-Notch-1. Both NeuroD and XASH-3 promote the expression of t he inhibitory ligand, X-Delta-l. However, XASH-3 appears to be sensiti ve to the inhibitory effects of X-Delta-l while NeuroD is much less so . Consequently only a subset of cells that ectopically express XASH-3 eventually form neurons, giving a scattered pattern, while the ectopic expression of NeuroD leads to a relatively dense pattern of ectopic n eurons. We propose that differences in the sensitivity of XASH-3 and N euroD to lateral inhibition play an important role during their respec tive roles in neuronal determination and differentiation.