A simple molecular model of neurulation.
A molecular model for the morphogenesis of the central nervous system is built and solved by computer. The formalism rests on molecular-biological data gathered from insects and vertebrates during neural differentiation and neuronal fate specification. Two genetic, hierarchically organized switches are introduced, one associated with f1p4al tissue formation, and the other with neuronal specification. The model switches evolve in time, setting up very similar "prepatterns" of genetic activity in both insects and vertebrates, as observed experimentally. We introduce the hypothesis that cell adhesion and motion are regulated by the switches. If cell motion is turned on by the neural switch, the whole neural tissue (neural plate) thickens, buckles, and folds, ultimately creating a closed neural tube (primary neurulation). When mitoses are more frequent in neural plate tissue, ingression of a neural cell mass takes place instead (secondary neurulation). If cell motions are controlled by the neuronal switch, rather than by the neural one, the differentiation of isolated neuroblasts is observed, which delaminate individually (as in insect neural cord formation). The model thus displays the three major known patterns of neurogenesis; the transition between the vertebrate and insect cases is predicted to result from changes in genetic regulation downstream of the switch genes, and affecting cell adhesion and motility properties. Little is known experimentally about the concerned pathways: their importance as a fruitful area for future investigation is emphasized by our theoretical results.
Kerszberg
M
M
Neurobiologie Moléculaire, Institut Pasteur, Paris, France.
Changeux
J P
JP
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002448:Cell Adhesion; D019070:Cell Lineage; D002465:Cell Movement; D002490:Central Nervous System / Q000196:embryology* / Q000254:growth & development; D002642:Chick Embryo; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology; D004475:Ectoderm / Q000166:cytology; D047108:Embryonic Development; D005326:Fetal Proteins / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007448:Invertebrates / Q000033:anatomy & histology / Q000196:embryology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice / Q000196:embryology; D008959:Models, Neurological; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000502:physiology; D009436:Neural Tube Defects / Q000196:embryology; D011506:Proteins / Q000502:physiology; D051880:Receptors, Notch; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology; D014714:Vertebrates / Q000033:anatomy & histology / Q000196:embryology; D014982:Xenopus laevis / Q000196:embryology
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005326:Fetal Proteins; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D051880:Receptors, Notch; D015534:Trans-Activators; D014157:Transcription Factors; C497759:N protein, Drosophila; C089199:ac protein, Drosophila; C064045:delta protein; C089197:sc protein, Drosophila