Neural induction Model organism: Xenopus

Late blastula neurula

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.

Two topics in this chapter are neural induction and axial formation

discovery of neural induction

Hensen’s node

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

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

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

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

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

Conserved between Drosophila and vertebrate

Polarity and establishment of the neuraxis

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

Where do signals come from?

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

Caveats of planar experiments 1. Can’t rule out vertical signals (cryptic gastrulation) 2. Deeper cells before gastrulation release cerberus

The two-signal model 1.General inducers: noggin, chordin, follistatin, induce anterior-like neural tissue, NCAM, Otx2, BF1. 2.Posterior factors 3.Anterior factors, Wnt vs. Wnt antagonist Source of inducers 1. Mesendoderm, anterior-to-posterior ingression posterior-to-anterior translocation 2. The organizer

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

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

Specific pathways for head induction Cerberus

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

Competence of the ectoderm

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

Mediolateral extent of the neural plate BMP conc gradient decides fate of epidermis, neural crest, neural plate. Experiments from zebrafish. epidermis neural crest neural plate BMP conc ENPNC

epidermis neural crest neural plate BMP conc ENPNC epidermis neural crest BMP conc ENPNC neural plate

ectoderm Neural plateNC Normal BMP2-/- Chordin-/- Chordin-/-, somitabun