1

The Mammalian Nervous

System

Development

2

Timing of embryological development

EventMouse Human

Size (mm)

daySize (mm)

day

Fertilization 1 0.1 - 0.15 1

Implantation of blastocyst 4.5 0.1 - 0.2 7-12

Appearance of primitive streak 7 0.2 13

Gastrulation starts; notochord appears

7.5

0.4 16

Neural plate and groove appear 1.0 – 1.5 18

First (1-3) somites & neuromeres (in hindbrain) appear 8 1.5 – 2.5 20

3

Timing of embryological development

EventMouse Human

Size (mm)

daySize (mm)

day

Neural tube starts to close (4-12 somites) 8 2.0 – 3.5 22

Cranial neuropore closes; optic vesicles appear (13-20

somites)

1.2 – 2.59 2.5 – 4.5 24

Caudal neuropore closes (somites; human 21-29; mouse 30-34)

3.3 – 3.9 10

3.0 – 5.0 26

Ventral and dorsal columns start to differentiate in spinal

cord and brain stem. Cranial nerve motor nuclei appear

(>30 somites)

4 – 6 28

Spinal nerves start to sprout, cerebral hemispheres

become visible3.5 – 4.9 10.5 5 – 7 32

Sensory and parasympathetic cranial nerve ganglia begin

to form5 – 6 11 7 – 9 33

Cerebellum starts to form 6 - 7 11.5 11 - 14 41

Gestation lasts 19-21 days for mice and about 266 days for humans

Fertilization

4

Formation of the blastocystWeek 1: human

5

Week 2

HumanSummary

6

Implantation and

formation of the

embryo

Implantation of the blastocyst

7

Germ disk

Formation of the yolk sac

8

Definitive yolk sac

Remnants of

primary yolk sac

Germ disk

Aminiotic

cavityAmniotic cavity

9

Week 3

HumanSummary

The primitive streak,

the notochord,

the neural plate and

first somites

Gastrulation.

Appearance of the

primitive streak

10

Primitive streak and the embryonic

mesoderm and endoderm:

Gastrulation

11

The ectoderm, the mesoderm and the

endoderm are all derived from the epiblast

The notochord

12

Cells entering into the mesodermal layer via the

primitive node form a tube (the notochordal process),

which is converted into a solid cylinder (the notochord)

after fusing transiently with the endoderm.

The notochord

The notochord contributes to the development

of the intervertebral discs

The notochord does NOT contribute to the

bone structure of the vertebrae

The notochord does NOT contribute to the

formation of the nervous system.

13

The somites

14

Cells entering the mesodermal layer via the primitive

groove and migrating laterally, form the paraxial,

intermediate and lateral plate mesoderms. The two

paraxial mesoderm columns (one on each side of the

midline) develop into somitomeres and then into somites.

Note: the first 7 (cranial) pairs of somatomeres do not form somites

Scanning electron microscopy

15

Notocord & somites

so

mit

es

Re

mo

ve

ec

tod

erm

Days 19 - 20

Fates of the somatomeres and somites

Somatomere pairs 1 – 7 (cranial region) Striated muscles of face, jaws & throat

Somite pairs 1 – 4 (occipital region)

(4 pairs)

Occipital bone of the skull, bones around the

nose, eyes and inner ears, extrinsic ocular

muscles and tongue muscles.

Somite pairs 5 – 12 (cervical region)

(8 pairs)

Occipital bone (somite pair 5)

Cervical vertebrae and associated muscles,

part of neck dermis and upper limb muscles

Somite pairs 13 – 24 (thoracic region)

(12 pairs)

Thoracic vertebrae and muscles and bones

of thoracic wall, part of thoracic dermis, part

of abdominal wall and upper limb muscles

Somite pairs 25 – 29 (lumbar region)

(5 pairs)

Lumbar vertebrae, abdominal muscles and

dermis, lower limb muscles.

Somite pairs 30 – 34 (sacral region)

(5 pairs)Sacrum and associated muscles and dermis

Somite pairs 35 – 37 (coccygeal region)

(3 pairs)Coccyx

Somite pairs 38 – 44 (embryonic tail region) Will degenerate later

16

Appearance

on

Day 20

~Day 30

Development of the nervous

system

17

From neural plate to neural groove

18

The prechordal plate

and the cranial portion

of the notochordal plate

induce the overlying

epiblast to differentiate

into a thick plate of

columnar, pseudo-

stratified

neuroepithelial cells, or

neurectoderm, called

the neural plate

First somites

appear in

mesodermal layer

Notochordal tube

fuses transiently

with the

endodermal layer

Notochordal

plate

Scanning electron microscopy

19

Neural plate & groove

Day 19 - 20

Weeks 4 & 5

Human

20

Neurulation

21

Neural crestNeural crest

Neural tube

notocord

Neurulation

22

The neural tube closes in

a zipper-like manner,

starting in the region of

the first 5 somites and

proceeding

bidirectionally.

Cellular structure of the

neural tube

23

Cells derived

from the

neural tube

24

Central canal

Fates of cells from the neural crest

25

Fates of

cells derived

from the

neural crest

26

Ganglion = a cluster of a

large number of neuronal

cell bodies outside of the

brain

Timeline of Spinal cord and

PNS development

27The neural crest plays a major role in PNS development

Formation of peripheral nerves

28

Peripheral nerves are

formed from cells

derived from both the

neural tube and the

neural crest

Sulcus

limitans

Roof plate

Floor

plate

Spinal nerve formation

29Spinal nerve

Vertebrae, peripheral nerves & muscles

30

The vertebrae and

skeletal muscles

are derived from the

somites

The notocord,

sclerotomes & the

vertebral column

31

32

Spinal cord

Timeline of brain development

33

cerebellum

pituitary

Glossary

34

Brain regionPrincipal

structuresOther features

Prosencephalon

(forebrain)

TelencephalonCerebral

hemispheres,

Hippocampus

Lateral ventricle, Choroid plexus,

Commissures connecting

hemispheres (e.g. corpus

callosum)

Diencephalon ThalamusThird ventricle, Choroid plexus,

Pituitary gland

Mesencephalon (midbrain)

Relay center between the

forebrain and the hindbrain and

spinal cord. Cerebral aquaduct

(between 3rd & 4th ventricles)

Rhombencephalon

(hindbrain)

MetencephalonCerebellum,

Pons

Pons relays signals between

spinal cord and cerebral and

cerebellar cortices

MyelencephalonMedulla

oblongata

Relay center between spinal

cord and higher brain centers

The Neural Plate

& Neurulation

35

36

The brain: growing & folding

The brain:

growing & folding

37

26 days

28 days

Future 4th

ventricle

Future pons

Med. Oblongata

cerebrum

Spinal cord

50 days

mes35 days

Midbrain

Future

cerebellum

Development of the

cerebellum

38

60 days

40 days

90 days

120 days150 days

The brain: growing & folding

39

mes

The cerebellum grows out

of the roof of the future

4th ventricle before it

closes

The telencephalon (future

cerebral hemispheres) grow up,

over and back over the

diencephalon (future [hypo-/epi-]

thalamus)

The brain and the embryo

40

41

Sources

• Human embryology. W. J. Larsen, 2nd edition,

1997 (publ. Churchill Livinstone Inc)

• An introduction to embryology. B. I. Balinski,

2nd edition,1970 (publ. W.B. Saunders Company)

• The house mouse: atlas of embryonic

development. K. Theiler, 1989 (publ. Springer-Verlag)

42