Talk:Neural - Cranial Nerve Development

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Cite this page: Hill, M.A. (2021, June 22) Embryology Neural - Cranial Nerve Development. Retrieved from

MeSH Terms: Cranial Nerves/embryology


Cranial Pair 0: The Nervus Terminalis

Anat Rec (Hoboken). 2019 Mar;302(3):394-404. doi: 10.1002/ar.23826. Epub 2018 May 17.

Peña-Melián Á1, Cabello-de la Rosa JP2, Gallardo-Alcañiz MJ2, Vaamonde-Gamo J2, Relea-Calatayud F3, González-López L3, Villanueva-Anguita P4, Flores-Cuadrado A4, Saiz-Sánchez D4, Martínez-Marcos A4.

Originally discovered in elasmobranchs by Fritsh in 1878, the nervus terminalis has been found in virtually all species, including humans. After more than one-century debate on its nomenclature, it is nowadays recognized as cranial pair zero. The nerve mostly originates in the olfactory placode, although neural crest contribution has been also proposed. Developmentally, the nervus terminalis is clearly observed in human embryos; subsequently, during the fetal period loses some of its ganglion cells, and it is less recognizable in adults. Fibers originating in the nasal cavity passes into the cranium through the middle area of the cribiform plate of the ethmoid bone. Intracranially, fibers joint the telencephalon at several sites including the olfactory trigone and the primordium of the hippocampus to reach preoptic and precommissural regions. The nervus terminalis shows ganglion cells, that sometimes form clusters, normally one or two located at the base of the crista galli, the so-called ganglion of the nervus terminalis. Its function is uncertain. It has been described that its fibers facilitates migration of luteinizing hormone-releasing hormone cells to the hypothalamus thus participating in the development of the hypothalamic-gonadal axis, which alteration may provoke Kallmann's syndrome in humans. This review summarizes current knowledge on this structure, incorporating original illustrations of the nerve at different developmental stages, and focuses on its anatomical and clinical relevance. Anat Rec, 302:394-404, 2019.

© 2018 Wiley Periodicals, Inc.

KEYWORDS: Kallmann's syndrome; gonadotropin-releasing hormone; luteinizing hormone-releasing hormone; olfactory placode PMID: 29663690 DOI: 10.1002/ar.23826


Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration

Biol Open. 2017 Oct 15;6(10):1528-1540. doi: 10.1242/bio.026153.

Simon E1, Thézé N1, Fédou S1, Thiébaud P1, Faucheux C2.

Abstract 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. Vgll3 interacts in the embryo with Tead proteins but unexpectedly with Ets1, with which it is able to stimulate a MCAT driven luciferase reporter gene. Our findings highlight a critical function for vgll3 in vertebrate early development. KEYWORDS: Cranial neural crest; Ets1; Trigeminal nerve; Vestigial-like; Wnt-FGF; Xenopus PMID: 28870996 PMCID: PMC5665465 DOI: 10.1242/bio.026153


Dynamic expression of transcription factor Brn3b during mouse cranial nerve development

J Comp Neurol. 2016 Apr 1;524(5):1033-61. doi: 10.1002/cne.23890. Epub 2015 Sep 29.

Sajgo S1,2, Ali S1, Popescu O2,3, Badea TC1.


During development, transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. Such a combinatorial code has been proposed for the differentiation of projection neurons of the somatic and visceral components of cranial nerves. It is possible that individual neuronal cell types are not specified by unique transcription factors but rather emerge through the intersection of their expression domains. Brn3a, Brn3b, and Brn3c, in combination with each other and/or transcription factors of other families, can define subgroups of retinal ganglion cells (RGC), spiral and vestibular ganglia, inner ear and vestibular hair cell neurons in the vestibuloacoustic system, and groups of somatosensory neurons in the dorsal root ganglia. The present study investigates the expression and potential role of the Brn3b transcription factor in cranial nerves and associated nuclei of the brainstem. 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. J. Comp. Neurol. 524:1033-1061, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. KEYWORDS: POU domain Brn3b; cranial nerves; facial nerve; glossopharyngeal nerve; optic nerve; transcription; trigeminal nerve; vagus nerve

PMID 26356988

G-Protein α-Subunit Gsα Is Required for Craniofacial Morphogenesis

PLoS One. 2016 Feb 9;11(2):e0147535. doi: 10.1371/journal.pone.0147535. eCollection 2016.

Lei R1,2,3, Zhang K1,2,3, Wei Y1, Chen M4, Weinstein LS4, Hong Y5, Zhu M3, Li H2, Li H1,3.


The heterotrimeric G protein subunit Gsα couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gsα is ubiquitously expressed in many cell types; however, the role of Gsα in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gsα knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsα knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsα knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsα in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsα is required for neural crest cells-derived craniofacial development. PMID 26859889


Cranial nerve development requires co-ordinated Shh and canonical Wnt signaling

PLoS One. 2015 Mar 23;10(3):e0120821. doi: 10.1371/journal.pone.0120821. eCollection 2015.

Kurosaka H1, Trainor PA2, Leroux-Berger M3, Iulianella A4.


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 signaling.

PMID 25799573


A fate-map for cranial sensory ganglia in the sea lamprey

Dev Biol. 2014 Jan 15;385(2):405-16.

Modrell MS, Hockman D, Uy B, Buckley D, Sauka-Spengler T, Bronner ME, Baker CV.


Cranial neurogenic placodes and the neural crest make essential contributions to key adult characteristics of all vertebrates, including the paired peripheral sense organs and craniofacial skeleton. Neurogenic placode development has been extensively characterized in representative jawed vertebrates (gnathostomes) but not in jawless fishes (agnathans). Here, we use in vivo lineage tracing with DiI, together with neuronal differentiation markers, to establish the first detailed fate-map for placode-derived sensory neurons in a jawless fish, the sea lamprey Petromyzon marinus, and to confirm that neural crest cells in the lamprey contribute to the cranial sensory ganglia. We also show that a pan-Pax3/7 antibody labels ophthalmic trigeminal (opV, profundal) placode-derived but not maxillomandibular trigeminal (mmV) placode-derived neurons, mirroring the expression of gnathostome Pax3 and suggesting that Pax3 (and its single Pax3/7 lamprey ortholog) is a pan-vertebrate marker for opV placode-derived neurons. Unexpectedly, however, our data reveal that mmV neuron precursors are located in two separate domains at neurula stages, with opV neuron precursors sandwiched between them. The different branches of the mmV nerve are not comparable between lampreys and gnatho-stomes, and spatial segregation of mmV neuron precursor territories may be a derived feature of lampreys. Nevertheless, maxillary and mandibular neurons are spatially segregated within gnathostome mmV ganglia, suggesting that a more detailed investigation of gnathostome mmV placode development would be worthwhile. Overall, however, our results highlight the conservation of cranial peripheral sensory nervous system development across vertebrates, yielding insight into ancestral vertebrate traits.

PMID 24513489


Neurosensory development and cell fate determination in the human cochlea

Neural Dev. 2013 Oct 16;8:20. doi: 10.1186/1749-8104-8-20.

Locher H, Frijns JH, van Iperen L, de Groot JC, Huisman MA, Chuva de Sousa Lopes SM1.


BACKGROUND: Hearing depends on correct functioning of the cochlear hair cells, and their innervation by spiral ganglion neurons. Most of the insight into the embryological and molecular development of this sensory system has been derived from animal studies. In contrast, little is known about the molecular expression patterns and dynamics of signaling molecules during normal fetal development of the human cochlea. In this study, we investigated the onset of hair cell differentiation and innervation in the human fetal cochlea at various stages of development. RESULTS: At 10 weeks of gestation, we observed a prosensory domain expressing SOX2 and SOX9/SOX10 within the cochlear duct epithelium. In this domain, hair cell differentiation was consistently present from 12 weeks, coinciding with downregulation of SOX9/SOX10, to be followed several weeks later by downregulation of SOX2. Outgrowing neurites from spiral ganglion neurons were found penetrating into the cochlear duct epithelium prior to hair cell differentiation, and directly targeted the hair cells as they developed. Ubiquitous Peripherin expression by spiral ganglion neurons gradually diminished and became restricted to the type II spiral ganglion neurons by 18 weeks. At 20 weeks, when the onset of human hearing is thought to take place, the expression profiles in hair cells and spiral ganglion neurons matched the expression patterns of the adult mammalian cochleae. CONCLUSIONS: Our study provides new insights into the fetal development of the human cochlea, contributing to our understanding of deafness and to the development of new therapeutic strategies to restore hearing.

PMID 24131517

Cranial neural crest cells form corridors prefiguring sensory neuroblast migration

Development. 2013 Sep;140(17):3595-600. doi: 10.1242/dev.091033.

Freter S1, Fleenor SJ, Freter R, Liu KJ, Begbie J.


The majority of cranial sensory neurons originate in placodes in the surface ectoderm, migrating to form ganglia that connect to the central nervous system (CNS). Interactions between inward-migrating sensory neuroblasts and emigrant cranial neural crest cells (NCCs) play a role in coordinating this process, but how the relationship between these two cell populations is established is not clear. Here, we demonstrate that NCCs generate corridors delineating the path of migratory neuroblasts between the placode and CNS in both chick and mouse. In vitro analysis shows that NCCs are not essential for neuroblast migration, yet act as a superior substrate to mesoderm, suggesting provision of a corridor through a less-permissive mesodermal territory. Early organisation of NCC corridors occurs prior to sensory neurogenesis and can be recapitulated in vitro; however, NCC extension to the placode requires placodal neurogenesis, demonstrating reciprocal interactions. Together, our data indicate that NCC corridors impose physical organisation for precise ganglion formation and connection to the CNS, providing a local environment to enclose migrating neuroblasts and axonal processes as they migrate through a non-neural territory. KEYWORDS: Cranial sensory ganglia; Neural crest; Placode

PMID 23942515


Placodal sensory ganglia coordinate the formation of the cranial visceral motor pathway

Dev Dyn. 2010 Apr;239(4):1155-61. doi: 10.1002/dvdy.22273.

Takano-Maruyama M1, Chen Y, Gaufo GO.

Abstract The parasympathetic reflex circuit is controlled by three basic neurons. In the vertebrate head, the sensory, and pre- and postganglionic neurons that comprise each circuit have stereotypic positions along the anteroposterior (AP) axis, suggesting that the circuit arises from a common developmental plan. Here, we show that precursors of the VIIth circuit are initially aligned along the AP axis, where the placode-derived sensory neurons provide a critical "guidepost" through which preganglionic axons and their neural crest-derived postganglionic targets navigate before reaching their distant target sites. In the absence of the placodal sensory ganglion, preganglionic axons terminate and the neural crest fated for postganglionic neurons undergo apoptosis at the site normally occupied by the placodal sensory ganglion. The stereotypic organization of the parasympathetic cranial sensory-motor circuit thus emerges from the initial alignment of its precursors along the AP axis, with the placodal sensory ganglion coordinating the formation of the motor pathway.

PMID 20235227

Epibranchial ganglia orchestrate the development of the cranial neurogenic crest

Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2066-71. doi: 10.1073/pnas.0910213107. Epub 2010 Jan 19.

Coppola E1, Rallu M, Richard J, Dufour S, Riethmacher D, Guillemot F, Goridis C, Brunet JF.


The wiring of the nervous system arises from extensive directional migration of neuronal cell bodies and growth of processes that, somehow, end up forming functional circuits. Thus far, this feat of biological engineering appears to rely on sequences of pathfinding decisions upon local cues, each with little relationship to the anatomical and physiological outcome. Here, we uncover a straightforward cellular mechanism for circuit building whereby a neuronal type directs the development of its future partners. We show that visceral afferents of the head (that innervate taste buds) provide a scaffold for the establishment of visceral efferents (that innervate salivatory glands and blood vessels). In embryological terms, sensory neurons derived from an epibranchial placode--that we show to develop largely independently from the neural crest--guide the directional outgrowth of hindbrain visceral motoneurons and control the formation of neural crest-derived parasympathetic ganglia.

PMID 20133851


Cranial nerve development: placodal neurons ride the crest

Curr Biol. 2002 Mar 5;12(5):R171-3.

Barlow LA.


Neurons of the vertebrate cranial sensory ganglia arise from both neural crest and a series of ectodermal thickenings termed neurogenic placodes. Recent results lend insight into how these two populations of cells coordinate their development, and subsequently innervate their central target, the hindbrain.

PMID 11882306


Anatomy and embryology of the trigeminal nerve and its branches in the parasellar area

Neurol Res. 1997 Feb;19(1):57-65.

Kehrli P1, Maillot C, Wolff MJ.


The cavum trigeminale (Meckel's cave) anatomy is still poorly understood. Many different descriptions are found in the literature. In order to clarify the relationship of trigeminal ganglion and its branches with dura and arachnoid, we underwent an embryological and adult microanatomical and histological study. Serial sections of human embryos and fetuses were used. For adult study, microdissections and histological serial sections were performed. We found that dura and arachnoid stop at the trigeminal ganglion and do not extend the three branches of the trigeminal nerve. These three branches are embedded into separate peripheral sheaths. These results are important for clear understanding of the anatomy of the parasellar lodge (cavernous sinus) lateral wall. PMID 9090638