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, Otx2Midbrain 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

E NPNC

epidermis

neural crest

neural plate

BMP conc

E NPNC

epidermis

neural crest

BMP conc

E NPNC

neural plate

ectoderm ectodermNeural plateNC NC

Normal

BMP2-/-

Chordin-/-

Chordin-/-,somitabun