Neural inductions

What is developmental plasticity?

The ability of early embryonic cells to adopt multiple possible fates.

How does developmental potential change during development?

Cells become progressively restricted in their developmental potential.

Is genetic information lost as cells differentiate?

No; differentiated nuclei can still generate full organisms (e.g., frog nuclear transplant experiments).

What causes cells to adopt different fates during development?

Differential gene expression and integration of internal and external signals.

What is neural induction?

The process by which ectodermal embryonic cells choose a neural fate instead of epidermal or mesodermal fate.

How did Claudio D. Stern define neural induction?

Ectodermal cells decide to acquire neural fate rather than forming epidermis or mesoderm.

What are the main topics in this lecture?

Gastrulation, organisers, fate maps, Xenopus, zebrafish, species conservation, neural inducer identification, default hypothesis, neural tube differentiation.

What is gastrulation?

Complex tissue movements that establish germ layers and position neurogenic regions.

Where does gastrulation begin in Xenopus?

At the involuting marginal zone (IMZ) or dorsal lip of the blastopore (DLB).

What germ layers are established during gastrulation?

Ectoderm, mesoderm, and endoderm.

What does neural induction produce in the embryo?

The neural plate.

What happens to the neural plate?

It undergoes morphogenetic movements to form the neural tube.

Who discovered the organizer?

Hilde Mangold and Hans Spemann (Spemann–Mangold organizer).

Why did Hilde Mangold not receive the Nobel Prize?

She died before the award; Nobel Prizes are not awarded posthumously.

What early work hinted at organizer-like activity before Spemann/Mangold?

Ethel Browne Harvey’s Hydra grafting experiments (1909).

What is the contemporary vertebrate developmental model organism?

Zebrafish.

What are key zebrafish early developmental movements?

Epiboly and convergence-extension.

What is "hpf"?

Hours post fertilization.

What does zebrafish neurulation show in imaging?

Dorsal–ventral spinal cord patterning visualized via ptch2:kaede signals and membrane markers.

What question arises from zebrafish shield transplant experiments?

Why is the induced axis not always complete?

What is the tail organizer?

A signaling region responsible for secondary neurulation in zebrafish.

What are the three germ layers across species?

Ectoderm, mesoderm, endoderm.

What does the ectoderm form?

Skin and nervous system.

What does the mesoderm form?

Musculoskeletal system, vasculature, reproductive and excretory systems.

What does the endoderm form?

Gut, lungs, liver, thyroid.

Is organizer activity conserved across species?

Yes; heterospecific organizers can induce secondary axes (e.g., zebrafish experiments).

When does the human neural tube appear?

During the 4th week after fertilisation.

What layer produces the CNS in humans?

The ectoderm.

How does the neural tube form in mammals?

Ectoderm folds into a tube under chemical signals.

What forms from the neural crest?

PNS structures.

What do somites form?

Bone and muscle.

What are neuropores?

Open ends of the neural tube that close by the end of the 4th week.

What defects arise from failed neural tube closure?

Anencephaly (no cerebrum) and spina bifida.

What condition results from severe brain tissue loss, leaving only the brain stem?

Hydranencephaly.

What question guides identification of neural inducers?

When and how ectoderm acquires neural fate.

What happens to animal caps isolated before gastrulation?

They develop into epidermis.

What happens to animal caps isolated during gastrulation?

They form neuronal tissue.

What does the animal cap assay show about mesoderm induction?

Mesoderm is induced by diffusible signals from vegetal cells.

Do isolated animal caps form neuroectoderm?

No; they require inductive signals.

How do we identify factors that directly induce neural fate?

By finding molecules that induce neural markers without inducing mesoderm markers.

What is Noggin?

A neural inducer identified in 1992 by Richard Harland’s group.

How was Noggin discovered?

Through rescuing UV-ventralized Xenopus embryos using cDNA from dorsalized embryos.

How is Noggin’s neural-inducing ability confirmed?

Adding Noggin to animal caps induces neural genes directly.

What is Chordin?

A neural inducer identified in 1994 by Eddy De Robertis’ group.

How was Chordin discovered?

By differential screening of dorsal vs. ventral lip tissue.

What does Chordin do?

Induces neural axis and has dorsal-specific expression.

What is Activin?

A TGFβ molecule identified in screens for mesoderm inducers.

What happens when Activin signaling is blocked with a truncated receptor?

Mesoderm does not form but neural tissue appears—without a neural inducer.

What is the Activin–Follistatin hypothesis?

Activin normally inhibits neural induction; blocking inhibition releases the default neural fate.

What is the Default Hypothesis?

The idea that ectodermal cells default to a neural fate unless inhibited by external signals.

What molecule acts as the inhibitor of the inhibitor?

Follistatin, which binds Activin.

What does Follistatin do?

Binds Activin (and BMP7), induces neural tissue, and can generate secondary axes.

What happens when animal cap cells are dissociated?

They express neural markers instead of epidermis.

What does the dissociation experiment suggest?

Cell–cell signaling inhibits default neural fate.

What does addition of BMP4 to dissociated animal caps cause?

Epidermal development.

What is BMP4’s role in neural induction?

It is a neural inhibitor.

What does the Default Model state?

Ectoderm will become neural unless BMP signals inhibit it.

What do Chordin, Noggin, and Follistatin have in common?

They are BMP antagonists released from the involuting mesoderm.

How do neural inducers work?

By binding and sequestering BMPs, preventing them from blocking neural fate.

Is neural induction explained solely by the Default Model?

No; Wnt/β-catenin and FGF pathways also play roles.

How does Wnt/β-catenin influence neural fate?

Induces neural fate by blocking BMP4 transcription in dorsal ectoderm.

What Wnt antagonists does the organizer secrete?

Frzb1, Cerberus, and Dkk1.

Is pre-gastrula FGF signalling required for neural fate?

Yes; FGF signalling is necessary for neural emergence.

Is neural induction a single pathway?

No; it relies on complex pathway interactions.

What happens during neural tube differentiation?

Neural tube forms primary vesicles which later subdivide.

What are the three primary brain vesicles?

Prosencephalon, mesencephalon, rhombencephalon.

What influences initial vesicle patterning?

A gradient of Wnt proteins.

What are the five secondary brain vesicles?

Telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon.

What structures develop from the telencephalon?

Cerebral cortex, basal ganglia, amygdala, and corpus callosum.

What structures develop from the diencephalon?

Thalamus, hypothalamus, internal capsule.

What does the mesencephalon contain?

The cerebral aqueduct connecting third and fourth ventricles.

What develops from the metencephalon?

Pons and cerebellum.

What develops from the myelencephalon?

Medulla.

What does the caudal neural tube form?

The spinal cord.