The Alzheimer-related gene presenilin-1 facilitates sonic hedgehog expression in Xenopus primary neurogenesis

We analyzed the influence of presenilins on the genetic cascades that contr ol neuronal differentiation in Xenopus embryos. Resembling sonic hedgehog ( shh) overexpression, presenilin mRNA injection reduced the number of N-tubu lin(+) primary neurons and modulated Gli3 and Zic2 according to their roles in activating and repressing primary neurogenesis, respectively. Presenili n increased shh expression within its normal domain, mainly in the floor pl ate, whereas an antisense X-presenilin-alpha morpholino oligonucleotide red uced shh expression. Both shh and presenilin promoted cell proliferation an d apoptosis, but the effects of shh were widely distributed, while those re sulting from presenilin injection coincided with the range of shh signaling . We suggest that presenilin may modulate primary neurogenesis, proliferati on, and apoptosis in the neural plate, through the enhancement of shh signa ling. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.