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  • Review Article
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Patterning and axon guidance of cranial motor neurons

Nature Reviews Neuroscience volume 8, pages 859–871 (2007)Cite this article

Key Points

  • Anatomically, in vertebrate embryos, cranial motor neurons develop in columns and eventually cluster to form nuclei in discrete regions of the midbrain and hindbrain (which together make up the brainstem). Motor neurons in the different cranial motor nuclei extend axons, forming the cranial nerves, to innervate muscles and parasympathetic ganglia in the head and neck.

  • The specification of the identity of cranial motor nuclei depends on transcription factors, such as those encoded by Hox and Nkx genes, which are expressed in rostrocaudal or dorsoventral domains in the neuroepithelium, respectively. These transcription factor 'codes' confer axon pathfinding behaviour, although the repertoires of receptors involved in this process remain to be characterized in many cases.

  • Diffusible axon guidance molecules, such as netrin 1, Slit proteins and Semaphorins, are involved in guiding cranial motor axons away from the midline and channelling them towards target muscles. Conversely, HGF derived from these muscles acts as a chemoattractant.

  • Several studies on congenital cranial dysinnervation disorders in humans have identified mutations in patterning and axon guidance and/or transport molecules.

Abstract

The cranial motor nerves control muscles involved in eye, head and neck movements, feeding, speech and facial expression. The generic and specific properties of cranial motor neurons depend on a matrix of rostrocaudal and dorsoventral patterning information. Repertoires of transcription factors, including Hox genes, confer generic and specific properties on motor neurons, and endow subpopulations at various axial levels with the ability to navigate to their targets. Cranial motor axon projections are guided by diffusible cues and aided by guideposts, such as nerve exit points, glial cells and muscle primordia. The recent identification of genes that are mutated in human cranial dysinnervation disorders is now shedding light on the functional consequences of perturbations of cranial motor neuron development.

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Figure 1: Cranial nerves in the chick embryo.
Figure 2: Motor neuron organization in the vertebrate brainstem.
Figure 3: Expression patterns of Hox genes in the vertebrate hindbrain.
Figure 4: Patterns of neural crest migration and branchial arch Hox gene expression in chick and mouse embryos.
Figure 5: Dorsoventral patterning of cranial motor neurons.

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Acknowledgements

Thanks to A. Lumsden and R. Knight for critical comments on the manuscript.

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  1. MRC Centre for Developmental Neurobiology, King's College, Guy's Campus, London, SE1 1UL, UK

    Sarah Guthrie

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Glossary

Neural tube

The primordium of the nervous system.

Floor plate

The ventral midline structure of the CNS. It has a role in patterning and axon guidance.

Branchial arches

Repeated bars of mesenchymal tissue that contribute to the lower jaw and neck; each contains a cartilaginous component, a muscular component, a nerve and an artery.

Basal plate

The ventral half of the neuroepithelium.

Alar plate

The dorsal half of the neuroepithelium.

Neuroepithelium

A part of the early nervous system that consists of dividing progenitors arranged in a columnar epithelium.

Homeobox

A conserved 180 base pair sequence that encodes homeodomain regions of proteins that are involved in binding to DNA and regulating transcription.

Cranial paraxial mesoderm

The population of mesoderm cells that originates adjacent to the brainstem and gives rise to many head muscles.

Sphenopalatine ganglion

A parasympathetic ganglion that is innervated by VM neurons of the facial nerve.

Rhombic lip

The structure at the dorsal extreme of the hindbrain.

Congenital fibromatosis of the extraocular muscles

(CFEOM). A group of congenital syndromes that involve cranial nerve miswiring and paralysis or paresis of the extraocular muscles, often associated with drooping of the upper eyelid.

Duane syndrome

A congenital eye movement disorder characterized by impeded horizontal eye movements that resut from miswiring of the eye muscles.

Horizontal gaze palsy with progressive scoliosis

(HGPPS). A rare congenital syndrome that is characterized by the absence of conjugate horizontal eye movements and by deformities in the spine.

Möbius syndrome

A rare congenital disorder caused by abnormal development of the cranial nerves, which results in paresis or paralysis of the facial muscles and, in some cases, other abnormalities.

Marcus Gunn syndrome

Also known as jaw-winking syndrome. It consists of an elevation or depression of the eyelid on chewing and/or suckling, and is thought to be caused by aberrant innervation of branches of the trigeminal and oculomotor nerves.

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Guthrie, S. Patterning and axon guidance of cranial motor neurons. Nat Rev Neurosci 8, 859–871 (2007). https://doi.org/10.1038/nrn2254

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