Fate Determination

forming the neural plate:

neural tube:

Neural crest:

neural crest is a group of cells that form along the edges of the neural tube

These cells migrate away

Forms along the dorsal edge of the neural tube

change into migratory cells through a process called EMT

process where cells change from a tight, stationary structure into a loose, moving one

Epithelial cells

Attached tightly to each other

Have strong cell–cell connections

The compressed star communicates between the three anchors before relaxing its form in order to migrate 

Mesenchymal cells

Can move freely

Neural crest cells start as part of the neural tube (epithelial tissue).
To become neural crest cells, they must leave the neural tube and migrate.

Neural crest cells migrate along specific  

Ventral path → sensory & autonomic neurons

ventral path goes downward and inward from the neural tube.

Heading from the neural tube down to the anchor

Signals guiding migration:

BMPs

BMPs are morphogens, meaning:

They create concentration gradients

BMP2

SMAD proteins are activated

SMADs enter the nucleus

binds BMP receptors

Ephrins

Ephrin signaling

Ephrins work through Eph receptors, and the signaling is bidirectional:

Forward signaling

Eph receptor on one cell receives signal

The ephrin ligand on the other cell also sends a signal back

So both cells can respond, not just one.

Ephrins are guidance molecules that help neural crest cells and nerves move correctly by creating boundaries and repulsion signals.

bidirectional signaling

The body is always present and communicates back and forth with the anchor 

the three anchors communicate with each other 

it goes from concentrated meaning short and powerful near its source as the neural tube relaxes becoming more detailed and then compressing again at the end. The end and the beginning line up

Retina and optic nerve

Ectoderm and neural induction

default:

High BMP signaling

Neural induction occurs when:

BMP is inhibited (Noggin, Chordin, Follistatin)

Result:

Ectoderm → neural plate → neural tube

How the neural plate forms:

Organizer (notochord / mesoderm) releases signals

BMP signaling is inhibited

Cells elongate and thicken

What the neural tube is:

hollow, cylindrical structure

Formed from the neural plate

Lined by neuroepithelial cells

The central cavity becomes the ventricular system and central canal

neuroepithelial cells are:

Columnar, polarized cells

Line the inside of the neural tube

Form a pseudostratified epithelium

Direct descendants of neural plate cells:

Pseudostratified appearance

Apical–basal polarity

Express early neural markers such as:

Sox1 / Sox2 / Sox3

Nestin

Pax6 (region-dependent)

Neural plate border (special ectoderm)

neural plate border, which gives rise to:

Neural crest cells

Sensory neurons

Autonomic neurons

Schwann cells

Melanocytes

This region requires intermediate BMP + Wnt signaling.

Turns ectoderm into neural tissue instead of skin

Key mechanisms

BMP inhibition (Noggin, Chordin, Follistatin)

Wnt inhibition for brain (DKK1, Cerberus)

Result

Formation of the neural plate

Neural tube formation

Fate determination (specification → commitment)

Differentiation – cells acquire mature structure and function

Migration & integration – cells wire into circuits

The cell’s fate is locked in

Example: it will become a motor neuron no matter where it’s placed

What controls fate determination?

not a single signal—it’s an intersection of influences.

Intrinsic factors (inside the cell)

transcription factors that regulate gene expression:

Neurogenin (Ngn1/2) → neuronal fate

Mash1 / Ascl1 → neural lineage commitment

Olig2 → oligodendrocyte vs motor neuron decisions

Pax6, Nkx2.2, FoxG1, etc. → regional identity

Extrinsic signals (environmental cues)

Notch signaling – maintains progenitor state, delays fate commitment

(Shh) – ventral neuron identity (e.g., motor neurons)

Wnt & BMP – dorsal identities, glial fate

FGFs – proliferation and fate bias

Epigenetic locking (the molecular “seal”)

Cells in different regions of the neural tube get different fates

Once fate is determined, epigenetic changes reinforce it:

fate determination encodes both:

Cell type

Circuit role

fate determination as:

narrowing of possibility into identity

Second Loop

Fate determination is when a young brain cell decides what it will become.

What controls fate determination?

Signals from the environment

Key signaling pathways:

Notch

Wnt

BMP

Certain genes turn on while others turn off, locking in the choice

Differentiation

Differentiation is not random. It is driven by layered signals:

Intrinsic factors (inside the cell)

Transcription factors (e.g. Neurogenin, NeuroD, Pax6)

Neural progenitor cells

Working within the inner ring 

Triangle in the middle of the inner ring 

neural stem cells

Neural progenitor cells

mature neurons or glia

Extrinsic factors (environment)

Morphogens are signaling molecules that form concentration gradients and tell cells what to become based on signal strength.

Inside the cell, the morphogen activates signaling pathways that change gene activity

BMP → SMAD activation

Wnt → β-catenin activation

FGF → MAPK/ERK activation

Synaptogenesis

a synapse is

It consists of:

Presynaptic terminal (axon end)

Synaptic cleft (gap)

Postsynaptic membrane (dendrite or cell body)

Steps of Synaptogenesis

They recognize each other using cell adhesion molecules.

molecules involved

Presynaptic

Synaptophysin

Synapsin

Vesicle proteins

Postsynaptic

Receptors (AMPA, NMDA, etc.)

PSD-95 (scaffolding protein)

Adhesion molecules

Neurexins (presynaptic)

Neuroligins (postsynaptic)

Synaptic pruning is the process where the brain removes extra or weak synapses to strengthen the most important connections.

Removes unnecessary connections

Strengthens useful connections