NEURULATION AND CRANIOFACIAL DEVELOPMENT LEARNING OUTCOMES 1 Describe

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

Neural Crest Cell Induction Fox. D 3, Slug Wnt 6, 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 The midbrain gives rise to the Mes-encephalon vesicle Mes- The hindbrain gives rise to the Met- and Myel-encephalon vesicles Di. Tel- 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/

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 Laryngo. Tracheal 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

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 5 3 4 CRANIAL NECK MUSCLES LARYNGEAL MUSCLES 3 III 2 TONGUE III 1 PHARYNGEAL MUSCLES FACIAL 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 1 st pharyngeal pouch) EXTERNAL EAR (from 1 st branchial cleft) AUDITORY TUBE (from 1 st 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 2 nd 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 Mc. Geady TA, Quinn PJ, Fitzpatrick ES, Ryan MT (2006) Veterinary embryology University of North Carolina web site: http: //www. med. unc. edu/embryo_images/