her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is atarget of NOTCH signalling

her4 encodes a zebrafish bHLH protein of the HAIRY-E(SPL) family. The gene is transcribed in a complex pattern in the developing nervous system and in the hypoblast. During early neurogenesis, her4 expression domains include the regions of the neural plate from which primary neurons arise, suggestin g that the gene is involved in directing their development, Indeed, misexpr ession of specific her4 variants leads to a reduction in the number of prim ary neurons formed. The amino-terminal region of HER4, including the basic domain, and the region between the putative helix IV and the carboxy-termin al tetrapeptide WRPW are essential for this effect, since HER4 variants lac king either of these regions are non-functional. However, the carboxy-termi nal WRPW itself is dispensable. We have examined the interrelationships bet ween deltaD, deltaA, notch1, her4 and neurogenin1 by means of RNA injection s, her4 is involved in a regulatory feedback loop which modulates the activ ity of the proneural gene neurogenin, and as a consequence, of deltaA and d eltaD. Activation of notch1 leads to strong activation of her4, to suppress ion of neurogenin transcription and, ultimately, to a reduction in the numb er of primary neurons. These results suggest that her4 acts as a target of notch-mediated signals that regulate primary neurogenesis.