Embryonic development of the nervous system

Cell fate specification

-first step of nervous system development

-first cell fate diversification in embryos is germ layer formation

Pluripotent embryonic stem cells

-arise from the zygote after fertilisation and rapid cell divisions; give rise to the three germ layers

Primitive streak

Groove in the midline of the embryo through which future endoderm and mesoderm cells ingress

Neural induction

-step after germ layer formation

-signalling from mesodermal cells turns ectoderm into neural ectoderm

Gastrula organiser

Small group of mesodermal cells that secrete neural-inducing signals

Hensen's node

The gastrula organiser in amniote embryos (birds, reptiles, mammals)[cite: 12]

Neural-inducing signals

Active inducers and inhibitors

FGFs

-Fibroblast Growth Factors

-active neural inducers

BMPs

-neural inhibitors

-Bone Morphogenetic Proteins

-inhibited by Chordin and Noggin (anti-BMPs)

Neuroectoderm

-embryonic neural stem cells

-ectoderm near Hensen's node turned by neural inducing signals (anti-BMPs and FGFs)

Neural plate

Established in the ectoderm by neural induction

Neurulation

The neural plate rolls up to form the neural tube

Neural tube

Progenitor of the entire CNS

Neural tube closure

-occurs first in the cervical region

-then "zips up" towards the anterior and posterior ends

Anterior and posterior neuropores

The two openings left as the tube zips up

when does anterior neuropore close

Closes around day 25

when does posterior neuropore close

Closes around day 28

diseases caused by defects of neural tube closure

-anencephaly

-craniorachischisis

-spina bifida

Symmetrical division (early)

Exponential growth of the progenitor pool

Asymmetrical division

Linear growth; produces a progenitor plus a postmitotic neuron

Symmetrical division (late)

End of growth; progenitors divide into postmitotic neurons or glial cells

Postmitotic

Describes the neurons and glial cells produced by the progenitor divisions[cite: 12]

Notch and Numb (fruit fly)

Molecules shown in the fruit fly example of symmetrical versus asymmetrical divisions

Signalling centres (secondary organisers)

Groups of cells in the neural tube that secrete factors such as SHH or FGF8[cite: 13]

Function of signalling centres

Ensure specific types of neurons differentiate in the correct locations in the neural tube

SHH

Sonic Hedgehog; secreted by signalling centres[cite: 13]

FGF8

Fibroblast Growth Factor 8; secreted by signalling centres

Dopaminergic neuron induction

The intersection of FGF8 and SHH signalling induces dopaminergic neurons in the ventral midbrain[cite: 13]

Growth cone

At the tip of dynamic neural extensions (neurites); navigates through embryonic neural tissue

Neurites

Dynamic neural extensions with growth cones at their tips[cite: 13]

Growth cone cytoskeleton

F-actin (green) and microtubules (red) in the lecture image

Guidepost signals

Signals that direct axons to the right target, shown with the visual system[cite: 13]

Retinal ganglion cells (RGCs)

Project axons that exit the eyeball as the optic nerve

Optic chiasm

Where optic nerves from both eyes cross; axons become re-mixed[cite: 13]

LGN

Nucleus in the thalamus where axons become un-mixed and synapse onto specific target cells arranged in layers

Visual pathway (labelled)

Optic nerve, optic chiasm, optic tract, LGN, optic radiation, striate (primary visual) cortex; also superior colliculi[cite: 13]

EphB

Receptor expressed by RGCs in the lateral (temporal) retina; not expressed in medial (nasal) RGCs

Netrin

ECM factor at the optic disc that attracts RGC axons[cite: 13]

Ephrin B

EphB ligand at the optic chiasm midline; a repellent. Temporal RGC axons turn away, nasal axons cross

Slit

Diffusible chemo-repellent behind the optic chiasm; pushes axons away from the chiasm towards their target

Embryonic brain vesicles

Predict adult anatomy[cite: 13]

Primary vesicles (3)

Forebrain, midbrain, hindbrain

Secondary vesicles (5)

Telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon[cite: 13]

Forebrain

Gives telencephalon and diencephalon

Hindbrain

Gives metencephalon and myelencephalon[cite: 13]

Telencephalon derivatives

Olfactory lobes (smell), hippocampus (memory storage), cerebrum (association, "intelligence")

Diencephalon derivatives

Retina (vision), epithalamus (pineal gland), thalamus (relay centre for optic and auditory neurons), hypothalamus (temperature, sleep and breathing regulation)

Mesencephalon derivative

Midbrain (fibre tracts between anterior and posterior brain, optic lobes and tectum)[cite: 13]

Metencephalon derivatives

Cerebellum (coordination of complex muscular movements), pons (fibre tracts between cerebrum and cerebellum, mammals only)

Myelencephalon derivative

Medulla (reflex centre of involuntary activities)[cite: 13]

Spinal cord

Shown continuing from the vesicles on the vesicle diagram

Emerging anatomy (chick stage HH10, about 1 1/2 days)

Labelled optic vesicle, forebrain, midbrain, somites and heart[cite: 13]

CNS origin

The neural tube is the progenitor of the entire CNS

PNS origin

The slides do not state the origin of the PNS (see note below)[cite: 14]

Neural tube defects

Defects of neural tube closure; cause anencephaly, craniorachischisis or spina bifida depending on location. Caused by genetic and environmental factors; folate helps prevent them

Anencephaly

Neural tube defect (rostral neuropore region)[cite: 14]

Craniorachischisis

Neural tube defect (labelled on the closure diagram)

Spina bifida

Neural tube defect (caudal neuropore region; open spina bifida labelled myelomeningocele; spinal dysraphism also labelled)[cite: 14]

Microcephaly

Caused by impaired neurogenesis; pre- and postnatal forms

Congenital microcephaly

Isolated, syndromes (e.g., Poland, Down, Edward, Patau), gene deletions (e.g., cri du chat), gene defects (e.g., Smith-Lemli-Opitz syndrome, HPE)[cite: 14]

Acquired microcephaly

Injuries (stroke, death of monozygotic twin), infections (toxoplasmosis, rubella, Zika virus)

Drug-related microcephaly

Fetal alcohol syndrome[cite: 14]

Other causes of microcephaly

Maternal malnutrition, diabetes, hyperthermia, placental insufficiency etc