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 control neuronal differentiation in Xenopus embryos. Resembling sonic hedgehog (shh) overexpression, presenilin mRNA injection reduced the number of N-tubulin+ primary neurons and modulated Gli3 and Zic2 according to their roles in activating and repressing primary neurogenesis, respectively. Presenilin increased shh expression within its normal domain, mainly in the floor plate, whereas an antisense X-presenilin-alpha morpholino oligonucleotide reduced shh expression. Both shh and presenilin promoted cell proliferation and apoptosis, but the effects of shh were widely distributed, while those resulting from presenilin injection coincided with the range of shh signaling. We suggest that presenilin may modulate primary neurogenesis, proliferation, and apoptosis in the neural plate, through the enhancement of shh signaling.
Paganelli
A R
AR
Laboratorio de Embriología Molecular, Instituto de Biología Celular y Neurociencias, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 3 degrees piso (1121), Buenos Aires, Argentina.
Ocaña
O H
OH
Prat
M I
MI
Franco
P G
PG
López
S L
SL
Morelli
L
L
Adamo
A M
AM
Riccomagno
M M
MM
Matsubara
E
E
Shoji
M
M
Affranchino
J L
JL
Castaño
E M
EM
Carrasco
A E
AE
D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D017209:Apoptosis; D016282:Aspartic Acid Endopeptidases; D002454:Cell Differentiation; D002455:Cell Division; D002490:Central Nervous System / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology*; D016376:Oligonucleotides, Antisense; D053764:Presenilin-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D000074290:Zinc Finger Protein Gli3
D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012333:RNA, Messenger; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D014404:Tubulin; D029867:Xenopus Proteins; C112757:Zic2 protein, Xenopus; D000074290:Zinc Finger Protein Gli3; D014212:Tretinoin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse