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.
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
Early ingressing cells become prechodal plate and induce forebrain. Late ingressing cells become notochord and induce midbrain, hindbrain, and spinal cord.
Holtfreter, urodele Xenopus, primitive induction OK and showed AP axis
Caveats of planar experiments Can’t rule out vertical signals (cryptic gastrulation) Deeper cells before gastrulation release cerberus
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
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
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 BMP conc neural crest neural plate E NC NP
epidermis BMP conc neural crest neural plate E NC NP epidermis BMP conc neural crest neural plate E NC NP
NC Neural plate NC ectoderm ectoderm Normal BMP2-/- Chordin-/- Chordin-/-, somitabun