A maternal Smad protein regulates early embryonic apoptosis in Xenopus laevis.
We identified cDNAs encoding the Xenopus Smad proteins most closely related to mammalian Smad8, and we present a functional analysis of this activity (also referred to recently as xSmad11). Misexpression experiments indicate that xSmad8(11) regulates pathways distinct from those regulated by the closely related xSmad1. Embryos that develop from eggs depleted of xSmad8(11) mRNA fail to gastrulate; instead, at the time of gastrulation, they initiate a widespread program of apoptosis, via a CPP32/caspase 3 pathway. Embryos that avoid this fate display gastrulation defects. Activation of apoptosis is rescued by expression of xSmad8(11) but not xSmad1. Our results demonstrate an embryonic requirement for Smad8(11) activity and show that a maternally derived Smad signaling pathway is required for gastrulation and for mediating a cell survival program during early embryogenesis. We suggest that xSmad8(11) functions as part of a maternally derived mechanism shown previously by others to monitor Xenopus early embryonic cell cycles.
Miyanaga
Yuko
Y
Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Torregroza
Ingrid
I
Evans
Todd
T
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D017124:Conserved Sequence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm; D005775:Gastrula / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D023121:RNA, Messenger, Stored / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051785:Smad Proteins; D051904:Smad8 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology*
D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D023121:RNA, Messenger, Stored; D051785:Smad Proteins; D051904:Smad8 Protein; C491622:Smad8 protein, Xenopus; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins