Download L7 Neurulation and nervous system

NEURULATION AND CRANIO-FACIAL DEVELOPMENT
LEARNING OUTCOMES
1. Describe the induction of the neural plate by the notochord and the progressive formation of
the neural tube
2. Explain the origin of the neural crest cells, their migration and eventual destinations
3. Show the segmental pattern of nerve development in the spinal cord and the relationship
between nerve, and muscle derived from the myotome
4. Outline the segmentation of the brain
5. Describe the congenital malformation of the nervous system, e.g. spinal bifida, cerebellar
hypoplasia and hydrocephalus.
6. Outline the development of the nasal passage and the mouth
7. Understand the development of the ear and the eye
The notochord induces the overlying neuroectoderm
cell layer to invaginate to form the neural tube
Presumptive
neural crest
Ectoderm
Notochord
Represents paracrine signals
Neural crest
Neural tube
Neural tube closure begins near the rostral
end of the embryo and progresses caudally
Neuro-epithelial layer already showing
signs of elongation of cells (notochord
not present)
Neural groove forming
Neural tube formed with overlying
ectoderm and underlying notochord
The neural fold closes from a starting cervical
location in both a rostral and caudal direction
Anterior
neuropore
Heart
Non-fused
neural folds
Foregut
Hindgut
Mouse 9 days
caudal neuropore
DORSAL VIEW
VENTRAL VIEW
Mouse 8 days
http://www.med.unc.edu/embryo_images/
Mouse 9 days
Neural crest cells escape the neuroectoderm
epithelium and migrate to diverse destinations
DESTINATIONS OF TRUNK NEURAL CREST CELLS
1
2
3
4
5
1. Melanocytes
2. dorsal root ganglion neurones
3. autonomic ganglia neurones
4. Adrenal medulla
5. Submucosal nerve plexus of gut
Neural crest cells leaving dorsal ectoderm
(Gilbert)
(Epithelial to mesenchyme transition)
Neural Crest Cell Induction
FoxD3, Slug
Wnt6, ectoderm
BMPs
Ectoderm
Neural crest precursors
Neural tube
Neural crest migration
• Slug activates factors inducing the dissociation of tight junctions
• Migrating cells follow cues from the extracellular matrix
• One set of proteins (fibronectin, laminin) promote migration while ephrin impedes
migration (remember lectures on cell adhesion and control of cell division)
The spinal cord develops a segmentation
pattern which reflects the pattern of somites.
SEGMENTATION IN THE SPINAL CORD AND PERIPHERAL NERVES
PIG - 38 DAYS
Dorsal root ganglion
PIG - TERM
Sensory neurone
Interneurone
Dorsal horn
Ventral horn
Motor efferent
Dermis
Muscle
A segmental reflex arc
Dorsal-ventral axis in the Neural Tube
TGFb family
in ectoderm
TGFb family
in roof plate
Gradient of
TGFb family
shh in
notochord
shh in
floor plate
shh
Gradient
of shh
Interneurones
Motor neurones
1. The notochord produces Sonic hedgehog (Shh) and induces the ventral neural tube to
become floor plate and produce Shh
2. The ectodermal cells produce members of the Transforming growth factor (TGF-b)
family and induce the dorsal neural tube to become roof plate and to start to produce the
same proteins
3. Two gradients are created of TGF-b and Shh
4. Different concentrations of these proteins activate the expression of different sets of
genes so that cells differentiate to become inter-neurones and motor neurones
The head also shows a rostral/caudal segmentation pattern but this
is less regular and more complex than that of the trunk somites
SEGMENTATION OF THE HEAD - REGIONS OF THE BRAIN
ANTERIOR NEUROPORE
FORE
MID
TELENCEPHALON
CEREBRAL HEMISPHERES
OLFACTORY LOBES
DIENCEPHALON
OPTIC VESICLES, PITUITARY,
HYPOTHALAMUS, THALAMUS
MESENCEPHALON
FIBRE TRACTS
BETWEEN ANTERIOR
AND POSTERIOR BRAIN
METENCEPHALON
CEREBELLUM MUSCULAR COORDINATION
PONS - FIBRE TRACTS
MYELVIII
METMES-
*
MYELENCEPHALON
VENTRICLES CONTAIN
CEREBROSPINAL FLUID
3 VESICLE STAGE
5 VESICLE STAGE
MEDULLA OBLONGATA INVOLUNTARY COORDINATION
DI-
II
TEL-
II AND VIII ARE CRANIAL NERVES INNERVATING OPTIC VESICLE
AND OTIC VESICLES RESPECTIVELY (CIRCLED)
* - THE NEUROHYPOPHYSIS WHICH GIVES RISE TO THE
NEURAL COMPONENT OF THE PITUITARY
SEGMENTATION OF THE HEAD
REGIONS OF THE BRAIN
The midbrain gives rise to the
Mes-encephalon vesicle
Mes-
The hindbrain gives rise to the
Met- and Myel-encephalon
vesicles
DiTel-
The forebrain gives rise to the
Tel- and Di-encephalon vesicles
Met-
Myel-
Faint evidence of
rhombomere
segmentation of metand myel-encephalon
Mouse 10 days. http://www.med.unc.edu/embryo_images/
CONGENITAL MALFORMATIONS OF BRAIN AND SPINAL CORD
1. Spina bifida
Teratogenic factors can block the induction by the underlying notochord of
the neural plate. This can lead to failure of closure of the neural tube in the
extreme form of Spina bifida
The development of the vertebral arches is disrupted and the arches fail to
fuse along the dorsal midline giving rise to an open vertebral canal
Normal
Spina bifida occulta
full Spina bifida
2. Exencephaly
Failure in the closure of the rostral neuropore
3. Cerebellar hypoplasia
Viral infection affects cerebellar development
4. Hydrocephalus
Poor circulation of cerebrospinal fluids in the aqueducts leads to cranial
accumulation and the pressure build-up leads to skull deformation and
neuroepithelial atrophy
The branchial arches are bilateral pouches of tissue separated
by branchial clefts in the region of the pharynx
Arch 1:
maxillary
Arch 1:
mandibular
Arch 1:
maxillary
Arch 2
Arch 3
Arch 1:
mandibular
Arch 2
Mouse, 10 days, lateral view
http://www.med.unc.edu/embryo_images/
Human, 30 days,
ventro-lateral view
The branchial arches are separated internally by pharyngeal
pouches and externally by branchial clefts
Mid-brain and vesicle
MIDLINE
Oral cavity
Torn edge of
oral plate
Floor of pharynx
1
2
3
Branchial arch
LaryngoTracheal
groove
Branchial cleft
Pharyngeal pouch
AORTIC ARCH
Mouse, 9 days, section, from dorsal view
http://www.med.unc.edu/embryo_images/
The branchial arches and clefts and the juxtaposed pharyngeal
pouches are a recapitulation of the respiratory anatomy of fish
There are 12 cranial nerves corresponding to the 7 somitomeres
and 5 rostral somites of the head region
SEGMENTATION OF THE HEAD - THE CRANIAL NERVES
GENERAL FEATURES
1. NERVES ORIGINATE IN BRAIN
12 CRANIAL
NERVES
2. OLFACTORY (I) AND OPTIC (II) ARE BRAIN
TRACTS RATHER THAN TRUE NERVES.
3. USUALLY LACK OF UNION OF DORSAL AND
VENTRAL ROOTS
4. MAY BE MOTOR OR SENSORY OR MIXED
CERVICAL NERVES
Motor cranial nerves follow their corresponding myotome to find their adult path
SEGMENTATION OF THE HEAD CRANIAL NERVES, MOTOR EFFERENTS AND TARGET MUSCLES
5 SOMITES
7 SOMITOMERES
IV
IX
VII 7
6
VI
5
V
4
XI
X
2
1
XII XII XII
5
3 4
CRANIAL NECK
MUSCLES
LARYNGEAL
MUSCLES
3
III 2
TONGUE
III 1
PHARYNGEAL
MUSCLES
FACIAL MUSCLES
MUSCLES OF
MASTICATION
EYE MUSCLES
ROMAN NUMERALS ARE THE CRANIAL MOTOR NERVES
ARROWS FROM SOMITOMERES AND SOMITES INDICATE THE MIGRATION OF THE
MYOBLASTS OF THE MYOTOME
SOME CRANIAL NERVES HAVE SENSORY AFFERENTS
I(OLFACTION), II(VISION), V(TOUCH), VII, IX, X (TASTE), VIII (HEARING AND BALANCE)
The bulges of the sensory ganglia of cranial nerves
innervating the branchial arches are visible on the surface
Arch 1:
maxillary
Surface bulge of sensory
ganglion of Cranial nerve
V (trigeminal)
Arch 1:
mandibular
Arch 2
Mouse, 10 days, lateral view
http://www.med.unc.edu/embryo_images/
Surface bulge of sensory
ganglion of Cranial nerve
VII (facial)
Cranial neural crest cells give rise to structural components
normally associated with the paraxial mesoderm in the trunk
SEGMENTATION IN THE HEAD
CRANIAL NEURAL CREST CELLS
DERIVATIVES IN
COMMON WITH
TRUNK NEURAL CREST
1. SENSORY AND AUTONOMIC NERVE
GANGLIA
2. SCHWANN CELLS OF PERIPHERAL
NERVES
3. MELANOCYTES
1.BONE, DERMIS OF FACE
2. MENINGES OF BRAIN
UNIQUE DERIVATIVES
3. CORNEA OF EYE
4. DENTAL PAPILLAE
5. CONNECTIVE TISSUE COMPONENTS
OF BRANCHIAL ARCHES
In the facial region, neural crest cells contribute all of the skeletal
and connective tissues with the exception of tooth enamel
Arrows indicate the origin and destinations
of neural crest cell populations.
http://www.med.unc.edu/embryo_images/
The branchial arches contribute to features of the face with their
tissue components deriving from both neural crest and myotome
FEATURES OF THE FACE AND THEIR ORIGINS - 1
1. Unusually, supporting tissue
components of branchial arches and
face derive from neural crest
EYE
NASAL PIT
MAXILLARY
DEVELOPMENT
(from arch 1)
STOMODEUM
(mouth)
TONGUE
MANDIBULAR
ARCH(arch 1)
(mastication)
HYOID ARCH (II)
(facial expression)
2. Muscle contribution is from
somitomeres
(for example somitomere 4 gives rise
to muscles of mastication)
3. Maxillary arch extends inwards to
fuse with its bilateral partner and the
nasal structures. It forms the bone of
the upper jaw and the tissues of the
upper lip
4. Mandibular arches fuse to form
lower jaw
5. Failure of fusion of maxillary arches
and nasal prominences gives rise to
cleft lip and palate
The epithelium of the oral cavity derives from both
ectodermal and endodermal sources
FEATURES OF THE FACE AND THEIR ORIGINS - 2
NASAL CAVITY
SECONDARY
PALATE
NASAL PIT
ORAL CAVITY
MANDIBULAR ARCH
TONGUE
TRACHEA
OESOPHAGUS
LUNG BUD
1. Lateral walls of nasal cavity contain olfactory epithelium
2. the rest of nasal cavity is pseudostratified ciliated epithelium derived from the original ectoderm
3. The oral cavity develops partly from ectoderm and partly from endoderm. The fusion point between the
two was the position of the (now degraded) oral plate
The otic placode is induced ectoderm which
invaginates to become the cavity of the inner ear
THE OTIC SENSORY PLACODES - 1
VIII
1. The otic placode invaginates to form the
otic vesicle which will become the inner ear
2. The splanchnopleure of the pharynx
forms a diverticulum - the first pharyngeal
pouch
II
NEURAL TUBE
(HINDBRAIN)
OTIC
PLACODE
NEURAL
GROOVE
NOTOCHORD
PHARYNX
Components of the middle and outer ear derive from
the first pharyngeal pouch and first branchial cleft
THE OTIC SENSORY PLACODES - 2
GANGLION OF CRANIAL NERVE VIII
OTIC VESICLE / INNER EAR (from otic placode)
BONES OF MIDDLE EAR (from 1st pharyngeal pouch)
EXTERNAL EAR (from 1st branchial cleft)
AUDITORY TUBE (from 1st pharyngeal pouch)
Fish have just the inner ear as an organ of
balance. The middle and outer ear evolved to
receive and transmit sound waves
(A)
9 day mouse
(B)
9 day mouse
The otic placode invaginates
to form an otic pit and finally
the otic vesicle. Its surface
aspect is dorsal to the 2nd
branchial cleft
http://www.med.unc.edu/embryo_images/
10 day mouse
The neural tube in the region of
the hindbrain induces
formation of the otic placode
(A) and then otic vesicle (B),
dorsolateral to the pharynx
The lens placode is induced ectoderm under the
influence of the neuroepithelium of the optic cup
THE DEVELOPMENT OF THE EYE - 1
ROSTRAL NEUROPORE
LENS PLACODE
FORE-BRAIN
LENS VESICLE
INNER/OUTER LAYERS OF OPTIC CUP
(this neuroepithelial layer gives rise to the
visual retina)
OPTIC STALK
The neuroepithelium gives rise to the pigmented
and neural retinal layers of the visual retina
THE DEVELOPMENT OF THE EYE - 2
PRESUMPTIVE
CORNEA
IRIS
PIGMENTED
RETINAL LAYER
TEMPORARY FUSION
OF EYELIDS
LENS
NEURAL
RETINAL LAYER
FIBRES OF
OPTIC NERVE
DEVELOPING EYELID
Neuroectoderm of optic vesicle inducing
surface ectoderm to form lens placode
The invaginating lens placode
pinches off to form the lens and
invagination of the optic vesicle
forms the optic cup connected to
the brain via the optic stalk
Mouse 8.5 days
Mouse 11 days
Mouse 10 days
http://www.med.unc.edu/embryo_images/
REFERENCES
Carlson BM (2003) Patten's Foundations of Embryology
Noden DM, de Lahunta (1985) A Embryology of domestic animals
McGeady TA, Quinn PJ, Fitzpatrick ES, Ryan MT (2006) Veterinary embryology
University of North Carolina web site: http://www.med.unc.edu/embryo_images/