The choice between epidermal and neural fate: a matter of calcium.
The development of the vertebrate embryo, which includes the induction and the patterning of the three germ layers, requires signaling among cells. In vertebrates, cells of the embryonic ectoderm have a choice during gastrulation between to fates; they give rise to epidermal progenitors on the ventral side and neural progenitors on the dorsal side. It was first shown by Spemann and Mangold in 1924 that the dorsal mesoderm (also called the Spemann-Mangold Organizer) has a potent biological capacity to induce nervous system from the adjacent ectoderm. A similar observation was reported in amniotes, indicating that neural induction by the Organizer is a conserved process controlling the initial steps in vertebrates neurogenesis. Molecular studies of the last decade have led to the identification of signaling molecules which participate in these embryonic decisions. Epidermis induction occurs through a signaling cascade involving Bone Morphogenetic Proteins (BMP 2, 4, 7) and receptor-regulated Smad proteins which translocate into the nucleus to form active transcriptional complexes. These molecules mediate BMPs effect to activate epidermal-specific gene expression and to repress neural-specific gene transcription. Neural fate is revealed by factors secreted by the dorsal mesoderm (Noggin, Chordin, Follistatin, ...) which act by blocking BMP signaling. Consequently, epidermal fate is an induced fate while neural fate is interpreted as a default state of the ectoderm. This review describes the signaling pathways which act to determine the fate of the ectoderm and discuss an alternative model in which neural fate is not a default state. This new model integrates the activation of a calcium-dependent signaling pathway due to an influx of calcium through L-type calcium channels. In this model, calcium plays a central regulatory role. While calcium is required for neural determination, epidermal determination occurs when calcium-dependent signaling pathways are inactive.
Equipe Biologie de la Différenciation Epithéliale, Institut Albert Bonniot, Université Joseph Fourier, Grenoble, France. moreau@cict.fr
Marc
M
Moreau
Catherine
C
Leclerc
D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D004475:Ectoderm / Q000166:cytology / Q000502:physiology; D004627:Embryonic Induction; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008954:Models, Biological; D009420:Nervous System / Q000196:embryology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D020746:Calcium Channels, L-Type; D014157:Transcription Factors; D002118:Calcium