Neural - Cranial Nerve Development

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Human Embryo CNS (stage 14) showing cranial nerve development
Cranial nerves
The cranial nerves (ganglia) are represented by a roman numeral (I - XII) and many have additional historic names. They are paired, and can be mixed (motor/sensory), and the brain equivalent of the spinal cord spinal nerves.

In embryonic development, the trigeminal ganglia (CN V, historically the semilunar ganglion, Gasser's ganglion or Gasserian ganglion) is the first to become apparent and is the largest of the cranial nerves.

Neural development is one of the earliest systems to begin and the last to be completed after birth. This development generates the most complex structure within the embryo and the long time period of development means in utero insult during pregnancy may have consequences to development of the nervous system.

Differences between birds and mammals:

  • both - have retinal axons projecting topographically to targets in the brain.
  • birds - the visual fibers from the entire retina decussate at the optic chiasm.
  • mammals - some axons from the temporal retina diverge at the midline to project ipsilaterally.

Neural development beginnings quite early, therefore also look at notes covering Week 3- neural tube and Week 4-early nervous system. Development of the neural crest and sensory systems (hearing/vision/smell) are only introduced in these notes and are covered in other notes sections.

Cranial Nerves
CN I Olfactory
CN II Optic
CN III Oculomotor
CN IV Trochlear
CN V Trigeminal
CN VI Abducent
CN VII Facial
CN VIII Acoustic
CN IX Glossopharyngeal
CN X Vagus
CN XI Accessory
CN XII Hypoglossal

Cranial Nerves 
Nerve Number Name Type Origin Function
CN I Olfactory sensory telencephalon smell placode
CN II Optic sensory retinal ganglial cells vision
CN III Oculomotor motor anterior midbrain extraocular muscles eye movements and pupil dilation (motor)
CN IV Trochlear motor dorsal midbrain extraocular muscles (superior oblique muscle)
CN V Trigeminal motor/sensory pons touch, mastication
CN VI Abducent motor extraocular muscles control eye movements (lateral rectus muscle)
CN VII Facial motor/sensory pons facial expression, taste (tongue anterior and central regions) regulate salivary production.
CN VIII Acoustic sensory vestibular and cochlear nuclei hearing, placode
CN IX Glossopharyngeal motor/sensory medulla swallowing and speech, taste (tongue posterior region)
CN X Vagus motor/sensory medulla larynx and pharynx muscles (speech and swallowing), regulates heartbeat, sweating, and peristalsis
CN XI Accessory motor motor neurons sternocleidomastoid and trapezius muscles
CN XII Hypoglossal motor motor neurons tongue muscles (speech, eating and other oral functions)

Cranial Nerve Links: Neural | Neural Crest | CN I | CN II | CN III| CN IV | CN V | CN VI | CN VII | CN VIII | CN IX | CN X | CN XI | CN XII | placodes | Category:Cranial Nerve
Historic Embryology Cranial Nerves 
1908 10 mm Human Embryo | 1912 Cerebral Nerves | 1925 Rat Ganglia | 1927 Oculomotor | 1938 Spinal Accessory | 1938 Hypoglossal | 1941 Olfactory | 1943 Oculomotor | 1947 Facial

Historic Embryology: 1908 Cranial Nerves 10 mm Human Embryo
Neural Links: ectoderm | neural | neural crest | ventricular | sensory | Stage 22 | gliogenesis | neural fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | neural abnormalities | folic acid | iodine deficiency | Fetal Alcohol Syndrome | neural postnatal | neural examination | Histology | Historic Neural | Category:Neural
Neural Parts: neural | prosencephalon | telencephalon cerebrum | amygdala | hippocampus | basal ganglia | diencephalon | epithalamus | thalamus | hypothalamus‎ | pituitary | pineal | mesencephalon | tectum | rhombencephalon | metencephalon | pons | cerebellum | myelencephalon | medulla oblongata | spinal cord | neural vascular | ventricular | lateral ventricles | third ventricle | cerebral aqueduct | fourth ventricle | central canal | meninges | Category:Ventricular System | Category:Neural

Some Recent Findings

Mouse cranial nerve model SHH[1]
  • Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration[2] "Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu, which mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila). In Drosophila, the Vestigial/Scalloped complex controls wing development by regulating the expression of target genes through binding to MCAT sequences. In vertebrates, there are four Vestigial-like genes, the functions of which are still not well understood. Here, we describe the regulation and function of vestigial-like 3 (vgll3) during Xenopus early development. A combination of signals, including FGF8, Wnt8a, Hoxa2, Hoxb2 and retinoic acid, limits vgll3 expression to hindbrain rhombomere 2. We show that vgll3 regulates trigeminal placode and nerve formation and is required for normal neural crest development by affecting their migration and adhesion properties. At the molecular level, vgll3 is a potent activator of pax3, zic1, Wnt and FGF, which are important for brain patterning and neural crest cell formation."
  • Dynamic expression of transcription factor Brn3b during mouse cranial nerve development[3] "During development, transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. ...We report the dynamic expression of Brn3b in the somatosensory component of cranial nerves II, V, VII, and VIII and visceromotor nuclei of nerves VII, IX, and X as well as other brainstem nuclei during different stages of development into adult stage. We find that genetically identified Brn3b(KO) RGC axons show correct but delayed pathfinding during the early stages of embryonic development. However, loss of Brn3b does not affect the anatomy of the other cranial nerves normally expressing this transcription factor."
  • Cranial nerve development requires co-ordinated Shh and canonical Wnt signaling[1] "Cranial nerves govern sensory and motor information exchange between the brain and tissues of the head and neck. The cranial nerves are derived from two specialized populations of cells, cranial neural crest cells and ectodermal placode cells. Defects in either cell type can result in cranial nerve developmental defects. Although several signaling pathways are known to regulate cranial nerve formation our understanding of how intercellular signaling between neural crest cells and placode cells is coordinated during cranial ganglia morphogenesis is poorly understood. Sonic Hedgehog (Shh) signaling is one key pathway that regulates multiple aspects of craniofacial development, but whether it co-ordinates cranial neural crest cell and placodal cell interactions during cranial ganglia formation remains unclear. In this study we examined a new Patched1 (Ptch1) loss-of-function mouse mutant and characterized the role of Ptch1 in regulating Shh signaling during cranial ganglia development. Ptch1(Wig/ Wig) mutants exhibit elevated Shh signaling in concert with disorganization of the trigeminal and facial nerves. Importantly, we discovered that enhanced Shh signaling suppressed canonical Wnt signaling in the cranial nerve region. This critically affected the survival and migration of cranial neural crest cells and the development of placodal cells as well as the integration between neural crest and placodes. Collectively, our findings highlight a novel and critical role for Shh signaling in cranial nerve development via the cross regulation of canonical Wnt singling."
More recent papers  
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Search term: Cranial Nerve Development

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

Neural Development Overview

Neuralation begins at the trilaminar embryo with formation of the notochord within the mesoderm that underlies the ectoderm and do not physically contribute to the nervous system, but is involved with patterning its initial formation. The central portion of the ectoderm then forms the neural plate that folds to form the neural tube, that will eventually form the entire central nervous system.

Early developmental sequence: Epiblast - Ectoderm - Neural Plate - Neural groove and Neural Crest - Neural Tube and Neural Crest

Neural Tube Development
Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
week 3 week 4 week 5 adult
neural plate
neural groove
neural tube

prosencephalon (forebrain) telencephalon Rhinencephalon, Amygdala, hippocampus, cerebrum (cortex), hypothalamus‎, pituitary | Basal Ganglia, lateral ventricles
diencephalon epithalamus, thalamus, Subthalamus, pineal, posterior commissure, pretectum, third ventricle
mesencephalon (midbrain) mesencephalon tectum, Cerebral peduncle, cerebral aqueduct, pons
rhombencephalon (hindbrain) metencephalon cerebellum
myelencephalon medulla oblongata, isthmus
spinal cord, pyramidal decussation, central canal

Embryonic Development

Cranial Nerve Development
Human Stage14 neural02.jpg Human Stage16 neural02.jpg
stage 14 stage 16


Developed from serially-sectioned human embryos[4]

  1. An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10.
  2. Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5.
  3. Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube.
  4. The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds.
  5. The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer.
  6. The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion.
  7. The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9-14.
  8. Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical.
  9. The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest.
  10. The hypoglossal crest provides cells that accompany those of myotomes 1-4 and form the hypoglossal cell cord at stages 13 and 14. # The occipital crest, which is related to somites 1-4 in the human, differs from the spinal mainly in that it does not develop ganglia.
  11. The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter.

Size Growth

Embryonic Central Nervous System
Stage 13 Stage 14 Stage 16 Stage 21
Human Stage13 sagittal upper half01.jpg

scale bar = 1 mm

Human Stage14 neural01.jpg Human Stage16 neural03.jpg Human Stage21 neural01.jpg
Week 4 Week 5 Week 6 Week 8

Human CNS Images: Carnegie stage 13 | Carnegie stage 13 label | Carnegie stage 14 | Carnegie stage 14 label | Carnegie stage 16 | Carnegie stage 16 label | CN V | Carnegie stage 21 lateral | Carnegie stage 21 median | Fetus CRL 240mm | Neural System Development | Cranial Nerves

Motor and Sensory

Cranial motor nerves brainstem nuclei of origin Primary Terminal Nuclei of the Afferent (sensory) Cranial Nerves
Cranial motor nerves brainstem nuclei of origin Primary Terminal Nuclei of the Afferent (sensory) Cranial Nerves

Pharyngeal Arches

During early development each pharyngeal arch is associated with different cranial nerves.

Arch Nerve  
  • Arch 1 - CN V trigeminal, caudal 2/3 maxillary (V2) and mandibular (V3), cranial 1/3 sensory nerve of head and neck, mastication motor
  • Arch 2 - CN VII facial
  • Arch 3 - CN IX glossopharyngeal
  • Arch 4&6 - CN X vagus, arch 4- superior laryngeal, arch 6- recurrent laryngeal

CN I Olfactory

Human week 10 fetus 12.jpg

Olfactory Nerve - Human fetus (Week 10)

  • sensory - olfactory receptor neuron axons
  • olfactory epithelium to cribriform plate of the ethmoid bone then to the olfactory bulb

Links: smell PubMed Search - CN I

CN II Optic

Based upon Streeter.[5]

  • Carnegie stage 19 - Optic nerve small, slender. Lumen practically whole length of stalk. Few or no fibers.
  • Carnegie stage 20 - Ependymal arrangement partially retained along stalk. Remnant of ependyma along whole length of stalk. Hyaloid groove at bulbar end. A few fibers arriving at brain.
  • Carnegie stage 21 - Remnant of ependyma present.
  • Carnegie stage 22 - Sheath layer beginning to form. Vascular canal present.
  • Carnegie stage 23 - Early nerve sheath. Reticular spongioblastic framework, striate arrangement of nuclei, bundles of fibers. Definite nerve sheath.

Stage 22 image 209.jpg

Optic Nerve - Human embryo (week 8, Carnegie stage 22)

  • sensory - retinal ganglion neuron axons
  • development - CNS out-pouching of the diencephalon (optic stalks)
  • optic nerve fibres covered with myelin produced by oligodendrocytes
  • ensheathed in all three meningeal layers (dura, arachnoid, and pia mater)
Links: vision

CN III Oculomotor

motor - innervates muscles that enable most eye movement

development - oculomotor nerve is derived from the basal plate of the embryonic midbrain

Links: vision
Historic Embryology  
Mann IC. The developing third nerve nucleus in human embryos (1927) J Anat. 61(4): 424-438. PubMed 17104156

CN IV Trochlear

motor - innervates the superior oblique muscle that enables eye movement

Cranial Nerve Rhombomere
trochlear 1
trigeminal 2–3
abducens 5–6
facial 4–5

See also the historic 1943 description of this cranial nerve development by Pearson.[6]

Links: vision

CN V Trigeminal

Mandibular division of the Trigeminal Nerve

(semilunar ganglion, Gasser's ganglion or Gasserian ganglion)

This is largest of all the cranial nerves during early development and has three major branches: ophthalmic nerve (V1), maxillary nerve (V2), mandibular nerve (V3)

Mixed motor/sensory

  • sensory - provide tactile, proprioceptive, and nociceptive afference to the face and mouth.
  • motor - innervate the skin of the face via ophthalmic (V1), maxillary (V2) and mandibular (V3) divisions. Special visceral efferent (SVE) axons innervate the muscles of mastication via the mandibular (V3) division.

Human Stage14-16 CN5-01.jpg

CN V Trigeminal week 5 Stage 14 and week 6 16

In the embryo, the trigeminal ganglia is first visible in week 4 stage 10, initially developing from neural crest cells before neural fold fusion, and after fusion receive contributions from the neural tube roof plate.[4]

In the adult, cavum trigeminale (Meckel's cave) is an arachnoidal pouch containing cerebrospinal fluid. Though the dura and arachnoid layers end at the trigeminal ganglion and do not extend to cover the three branches of the trigeminal nerve.[7]

Gasser's ganglion or Gasserian ganglion

This historic terminology was given by Antonius Hirsh who described the ganglion in 1765 and then named the ganglion in the honour of his teacher, Johann Lorenz Gasser (1723-1765) an Austrian anatomist.

CN VI Abducent

motor - innervates the lateral rectus muscle that enables eye movement

development - from the basal plate of the embryonic pons

Links: vision

CN VII Facial

(N. Facialis; Seventh Nerve; CN VII)

Mixed motor/sensory
  • motor - innervates the muscles of facial expression
  • sensory - taste from the anterior two-thirds of the tongue and oral cavity

Development - second pharyngeal arch

  • motor derived from the basal plate of the embryonic pons
  • sensory derived from cranial neural crest
Links: vision | taste

Gray Fig. 788. Plan of the Facial and Intermediate Nerves and their Communication with Other Nerves

The facial nerve (Figs. 788, 790) consists of a motor and a sensory part, the latter being frequently described under the name of the nervus intermedius (pars intermedii of Wrisberg) (Fig. 788). The two parts emerge at the lower border of the pons in the recess between the olive and the inferior peduncle, the motor part being the more medial, immediately to the lateral side of the sensory part is the acoustic nerve.

Streeter1908 fig02.jpg

Facial nerve development - right facial nerve and its nucleus of origin (A. 10 mm embryo, C. neonate).[8]

Geniculate ganglion - contains fibres for taste and somatic sensation and is located in the petrous temporal bone.

CN VIII Vestibulocochlear

Cranial nerve eight (CN VIII) In the embryo, cells derive from the otic placode forming the otic vesicle (otocyst). Ganglion previously thought to also involve otic neural crest (rhombomere 4)[4], but recent studies suggest an entirely placodal origin. In the adult, as in its name it consists of 2 parts vestibular (balance and position in space) and cochlear (hearing, spiral).

Adult hearing embryonic origins.jpg

Links: hearing | balance

Week 5 Week 8
Stage13 otocyst.jpg

Embryo Stage 13 showing inner ear and CN VIII.

Stage22 ear.jpg

Embryo Stage 22 showing otocyst and CN VIII.

Scarpa's ganglion

The historic name for the vestibular ganglion, also called is the ganglion of the vestibular nerve.

Links: hearing | balance

CN IX Glossopharyngeal

Baroreceptor reflex CN IX, X[9]

Mixed motor/sensory and lies anterior to the medulla oblongata

  • Branchial motor (special visceral efferent) – supplies the stylopharyngeus muscle.
  • Visceral motor (general visceral efferent) – provides parasympathetic innervation of the parotid gland via the otic ganglion.
  • Visceral sensory (general visceral afferent) – carries visceral sensory information from the carotid sinus and carotid body.

General sensory (general somatic afferent) – provides general sensory information from inner surface of the tympanic membrane, upper pharynx (GVA), and the posterior one-third of the tongue.

Visceral afferent (special visceral afferent) – provides taste sensation from the posterior one-third of the tongue, including circumvallate papillae.

CN X Vagus

(pneumogastric nerve) responsible for heart rate, gastrointestinal peristalsis, sweating, and muscle movements in the mouth, including speech (via the recurrent laryngeal nerve)


  • motor derived from the basal plate of the medulla oblongata
  • sensory derived from cranial neural crest

CN XI Accessory

motor - innervates the sternocleidomastoid and trapezius muscles

  • sternomastoid - muscle superficial layer side of the neck, rotation of the head
  • trapezius - superficial muscles from occipital bone to the lower thoracic vertebrae and laterally to the spine of the scapula, move the scapulae and support the arm.

See also the historic 1938 description of this cranial nerve development by Pearson.[10]

CN XII Hypoglossal

Human week 10 fetus 04.jpg
  • motor - hypoglossal nucleus of the ventromedial medulla oblongata from a number of smaller rootlets
  • development - basal plate of the medulla oblongata
Links: tongue | 1910 Pig hypoglossal ganglia development

Neonatal - Clinical

Examination of the baby’s cranial nerve function is often accomplished by observing spontaneous activity.

Newborn - Cranial Nerves
Newborn n 02.jpg
 ‎‎Cranial Nerves
Page | Play
Newborn ab 02.jpg
 ‎‎Cranial Nerves
Page | Play
Normal Abnormal

Cranial Nerve Development: 3 months | 12 months | 18 months

Links: Neural Exam Movies | Neonatal Development

Additional Images

Historic Images

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Thyng FW. The anatomy of a 17.8 mm human embryo. (1914) Amer. J Anat. 17: 31-112. Harvard Collection


  1. 1.0 1.1 Kurosaka H, Trainor PA, Leroux-Berger M & Iulianella A. (2015). Cranial nerve development requires co-ordinated Shh and canonical Wnt signaling. PLoS ONE , 10, e0120821. PMID: 25799573 DOI.
  2. Simon E, Thézé N, Fédou S, Thiébaud P & Faucheux C. (2017). Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration. Biol Open , 6, 1528-1540. PMID: 28870996 DOI.
  3. Sajgo S, Ali S, Popescu O & Badea TC. (2016). Dynamic expression of transcription factor Brn3b during mouse cranial nerve development. J. Comp. Neurol. , 524, 1033-61. PMID: 26356988 DOI.
  4. 4.0 4.1 4.2 O'Rahilly R & Müller F. (2007). The development of the neural crest in the human. J. Anat. , 211, 335-51. PMID: 17848161 DOI.
  5. Streeter GL. Developmental Horizons In Human Embryos Description Or Age Groups XIX, XX, XXI, XXII, And XXIII, Being The Fifth Issue Of A Survey Of The Carnegie Collection. (1957) Carnegie Instn. Wash. Publ. 611, Contrib. Embryol., 36: 167-196.
  6. Pearson AA. The trochlear nerve in human fetuses. (1943) J Comp. Neurol. : 29-43.
  7. Kehrli P, Maillot C & Wolff MJ. (1997). Anatomy and embryology of the trigeminal nerve and its branches in the parasellar area. Neurol. Res. , 19, 57-65. PMID: 9090638
  8. Streeter GL. The nuclei of origin of the cranial nerves in the 10 mm human embryo. (1908) Amer. J Anat. 2:111 - 115.
  9. 9.0 9.1 McNeill EM, Roos KP, Moechars D & Clagett-Dame M. (2010). Nav2 is necessary for cranial nerve development and blood pressure regulation. Neural Dev , 5, 6. PMID: 20184720 DOI.
  10. Pearson AA. The spinal accessory nerve in human embryos. (1938) J Comp. Neurol. 68(2): 243-266.


Greene ND & Copp AJ. (2009). Development of the vertebrate central nervous system: formation of the neural tube. Prenat. Diagn. , 29, 303-11. PMID: 19206138 DOI.

Barlow LA. (2002). Cranial nerve development: placodal neurons ride the crest. Curr. Biol. , 12, R171-3. PMID: 11882306


Saitsu H & Shiota K. (2008). Involvement of the axially condensed tail bud mesenchyme in normal and abnormal human posterior neural tube development. Congenit Anom (Kyoto) , 48, 1-6. PMID: 18230116 DOI.

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