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.

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

NEURULATION AND CRANIO-FACIAL DEVELOPMENT

Ectoderm

Presumptive neural crest

Notochord

The notochord induces the overlying neuroectoderm cell layer to invaginate to form the neural tube

Represents paracrine signals

Neural tube

Neural crest

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

DORSAL VIEW

http://www.med.unc.edu/embryo_images/

VENTRAL VIEW

Heart

Foregut

Hindgut

Non-fusedneural folds

Mouse 8 days

Mouse 9 days

Anterior neuropore

Mouse 9 days

caudal neuropore

The neural fold closes from a starting cervical location in both a rostral and caudal direction

Neural crest cells escape the neuroectoderm epithelium and migrate to diverse destinations

Neural crest cells leaving dorsal ectoderm (Gilbert)(Epithelial to mesenchyme transition)

DESTINATIONS OF TRUNK NEURAL CREST CELLS

1. Melanocytes 2. dorsal root ganglion neurones 3. autonomic ganglia neurones 4. Adrenal medulla 5. Submucosal nerve plexus of gut

1 2

3

54

FoxD3, Slug

Wnt6, ectoderm

BMPs

Neural Crest Cell Induction

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

Motor efferent

Dorsal horn

Ventral horn

PIG - TERM

Dermis

Muscle

A segmental reflex arc

Sensory neurone

Inter- neurone

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-) family and induce the dorsal neural tube to become roof plate and to start to produce the same proteins3. Two gradients are created of TGF- 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

TGF family in ectoderm

TGF family in roof plate

shh in notochord

shh in floor plate

Gradient of TGF family

Gradient of shh

Interneurones

Motor neuronesshh

Dorsal-ventral axis in the Neural Tube

The head also shows a rostral/caudal segmentation pattern but this is less regular and more complex than that of the trunk somites

3 VESICLE STAGE 5 VESICLE STAGE

CEREBRAL HEMISPHERES OLFACTORY LOBES

OPTIC VESICLES, PITUITARY, HYPOTHALAMUS, THALAMUS

FIBRE TRACTS BETWEEN ANTERIOR AND POSTERIOR BRAIN

CEREBELLUM - MUSCULAR COORDINATION PONS - FIBRE TRACTS

MEDULLA OBLONGATA - INVOLUNTARY COORDINATION

SEGMENTATION OF THE HEAD - REGIONS OF THE BRAIN

TEL-

DI-

MES-

MET-

MYEL-

II

VIII

*

FORE

MID

TELENCEPHALON

DIENCEPHALON

MESENCEPHALON

METENCEPHALON

MYELENCEPHALON

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

ANTERIOR NEUROPORE

VENTRICLES CONTAIN CEREBROSPINAL FLUID

SEGMENTATION OF THE HEAD REGIONS OF THE BRAIN

Mouse 10 days. http://www.med.unc.edu/embryo_images/

Faint evidence of rhombomere segmentation of met- and myel-encephalon

Di-

Tel-

The forebrain gives rise to the Tel- and Di-encephalon vesicles

Mes-The midbrain gives rise to the Mes-encephalon vesicle

Met-

Myel-

The hindbrain gives rise to the Met- and Myel-encephalon vesicles

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 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

Normal Spina bifida occulta full Spina bifida

Mouse, 10 days, lateral view

Arch 1: maxillary

Arch 1: mandibular

Arch 2

Human, 30 days, ventro-lateral view

Arch 1: maxillary

Arch 1: mandibular

Arch 2

Arch 3

The branchial arches are bilateral pouches of tissue separated by branchial clefts in the region of the pharynx

http://www.med.unc.edu/embryo_images/

Mouse, 9 days, section, from dorsal view

Mid-brain and vesicle

Oral cavity

Torn edge of oral plate

The branchial arches are separated internally by pharyngeal pouches and externally by branchial clefts

http://www.med.unc.edu/embryo_images/

AORTIC ARCH

MIDLINE

Laryngo-Trachealgroove

Floor of pharynx

1

2

3

Branchial arch

Branchial cleft

Pharyngeal pouch

SEGMENTATION OF THE HEAD THE BRANCHIAL ARCHES AND PHARYNGEAL POUCHES

EACH BRANCHIAL ARCH CONTAINS A CRANIAL NERVE AND AN AORTIC ARCH

THE FOUR PHARYNGEAL POUCHES CORRESPOND TO THE FOUR BRANCHIAL CLEFTS LATERALLY

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

12 CRANIAL NERVES

GENERAL FEATURES

1. NERVES ORIGINATE IN BRAIN 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

SEGMENTATION OF THE HEAD - THE CRANIAL NERVES

1

2

3

45

67

12

3 4 5

EYE MUSCLES

MUSCLES OF MASTICATION

FACIAL MUSCLES

PHARYNGEAL MUSCLES

CRANIAL NECK MUSCLES

LARYNGEAL MUSCLES

SEGMENTATION OF THE HEAD - CRANIAL NERVES, MOTOR EFFERENTS AND TARGET MUSCLES

TONGUE

7 SOMITOMERES

5 SOMITES

XIIXIIXIIXI

XIX

VIIVI

V

IV

III

III

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)

Motor cranial nerves follow their corresponding myotome to find their adult path

Mouse, 10 days, lateral view

Arch 1: maxillary

Arch 1: mandibular

Arch 2

Surface bulge of sensory ganglion of Cranial nerve V (trigeminal)

Surface bulge of sensory ganglion of Cranial nerve VII (facial)

The bulges of the sensory ganglia of cranial nerves innervating the branchial arches are visible on the surface

http://www.med.unc.edu/embryo_images/

SEGMENTATION IN THE HEAD CRANIAL NEURAL CREST CELLS

DERIVATIVES IN COMMON WITH TRUNK NEURAL CREST UNIQUE DERIVATIVES

1. SENSORY AND AUTONOMIC NERVE GANGLIA 2. SCHWANN CELLS OF PERIPHERAL NERVES 3. MELANOCYTES

1.BONE, DERMIS OF FACE 2. MENINGES OF BRAIN 3. CORNEA OF EYE 4. DENTAL PAPILLAE 5. CONNECTIVE TISSUE COMPONENTS OF BRANCHIAL ARCHES

Cranial neural crest cells give rise to structural components normally associated with the paraxial mesoderm in the trunk

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/

EYE NASAL PIT MAXILLARY DEVELOPMENT (from arch 1) STOMODEUM (mouth) TONGUE MANDIBULAR ARCH(arch 1) (mastication) HYOID ARCH (II) (facial expression)

FEATURES OF THE FACE AND THEIR ORIGINS - 1

1. Unusually, supporting tissue components of branchial arches and face derive from neural crest 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 branchial arches contribute to features of the face with their tissue components deriving from both neural crest and myotome

NASAL PIT

LUNG BUD

MANDIBULAR ARCH TONGUE

NASAL CAVITY SECONDARY PALATE ORAL CAVITY TRACHEA OESOPHAGUS

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

FEATURES OF THE FACE AND THEIR ORIGINS - 2

The epithelium of the oral cavity derives from both ectodermal and endodermal sources

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

THE OTIC SENSORY PLACODES - 1

NEURAL GROOVE

OTIC PLACODE

NOTOCHORD

NEURAL TUBE (HINDBRAIN)

PHARYNX

II

VIII

The otic placode is induced ectoderm which invaginates to become the cavity of the inner ear

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)

(B)

9 day mouse

10 day mouse

9 day mouse

http://www.med.unc.edu/embryo_images/

The otic placode invaginates to form an otic pit and finally the otic vesicle. Its surface aspect is dorsal to the 2nd branchial cleft

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 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 lens placode is induced ectoderm under the influence of the neuroepithelium of the optic cup

THE DEVELOPMENT OF THE EYE - 2

PRESUMPTIVE CORNEA IRIS

TEMPORARY FUSION OF EYELIDS

LENS

PIGMENTED RETINAL LAYER

NEURAL RETINAL LAYER

FIBRES OF OPTIC NERVE

DEVELOPING EYELID

The neuroepithelium gives rise to the pigmented and neural retinal layers of the visual retina

Mouse 8.5 days

http://www.med.unc.edu/embryo_images/

Mouse 11 days

Mouse 10 days

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

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/

REFERENCES