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Neural induction

Neural induction. Model organism: Xenopus. Late blastula. neurula.

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Neural induction

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  1. Neural induction Model organism: Xenopus

  2. Late blastula neurula

  3. P31. During gastrulation, tissue interaction between the involuting dorsal cells (prospective pharyngeal endoderm and dorsal mesoderm, collectively referred to as mesendoderm) and the overlying ectoderm define the region of the ectoderm that will form the nervous system and establish principal axes, and direct cells within this region towards a neural fate. This process is known as neural induction.

  4. Two topics in this chapter are neural induction and axial formation

  5. discovery of neural induction

  6. Hensen’s node

  7. Organizer releases inductive signals. All ectoderm are competent. Polarity has been determined.

  8. Search for the inducers Animal cap experiment, artificial inducers, 60 years pass

  9. Dissociated cells neurons (neural default) Dominant negative experiments Activins, Vg-1 BMPs Activins, inhibins Homodimer, hetrodimers Promiscuous receptors

  10. BMP2, BMP4, BMP7 Noggin, chordin, follistatin induce primitive neural tissue BMP inactivation triggers early neural markers, other factors are required to elicit differentiated markers

  11. WNTs as another class of neural inhibitors in animal cap explants.

  12. Conserved between Drosophila and vertebrate

  13. Polarity and establishment of the neuraxis

  14. Early ingressing cells become prechodal plate and induce forebrain. Late ingressing cells become notochord and induce midbrain, hindbrain, and spinal cord.

  15. Where do signals come from?

  16. Holtfreter, urodele Xenopus, primitive induction OK and showed AP axis

  17. Caveats of planar experiments Can’t rule out vertical signals (cryptic gastrulation) Deeper cells before gastrulation release cerberus

  18. The two-signal model General inducers: noggin, chordin, follistatin, induce anterior-like neural tissue, NCAM, Otx2, BF1. Posterior factors Anterior factors, Wnt vs. Wnt antagonist Source of inducers 1. Mesendoderm, anterior-to-posterior ingression posterior-to-anterior translocation 2. The organizer

  19. Posteriorizing signals (transforming signals) • Retinoic acid (constitutive and dominant-negative receptors) • FGF (avian beads) • Wnt • TGF members • Animal cap assay, beads

  20. Posteriorizing signals (transforming signals) • Retinoic acid (constitutive and dominant-negative receptors) • FGF (avian beads) • Wnt • TGF members • Animal cap assay, beads Forebrain marker: BF1, Otx2 Midbrain marker: Otx2, Engrail Hindbrain marker: Hox, Krox20

  21. Specific pathways for head induction Cerberus

  22. Dickkopf • In presumptive prechordal plate • Antagonist of Wnt Activin and nodal-related factors induce posteriorization in zebrafish Antivin converts posterior CNS into anterior

  23. Competence of the ectoderm

  24. Neural induction in the amniote embryo In mouse, the anteriormost region of the neural axis is induced by signals from presumptive extraembryonic (visceral) endoderm. Two effects of Otx2: induction, maintenance

  25. Mediolateral extent of the neural plate • BMP conc gradient decides fate of epidermis, neural crest, neural plate. Experiments from zebrafish. epidermis BMP conc neural crest neural plate E NC NP

  26. epidermis BMP conc neural crest neural plate E NC NP epidermis BMP conc neural crest neural plate E NC NP

  27. NC Neural plate NC ectoderm ectoderm Normal BMP2-/- Chordin-/- Chordin-/-, somitabun

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