The developmental logic of trigeminal sensory neurons

Lead Research Organisation: King's College London
Department Name: Developmental Neurobiology


Sensory neurons relay information about our external environment to our central nervous system. The sensory neurons that project to our face and jaws, form part of trigeminal nerve, whose name derived from the fact that it has 3 branches; one branch projects to the forehead region, one to the upper jaw and one to the lower jaw. Many of these neurons are concerned with relaying information about heat, pain, and touch from the head to brain. Another group of trigeminal sensory neurons is additionally concerned with spatial information about the position of our jaw, which is important for mastication and speech. This same situation is seen in all jawed vertebrates.

We know a lot about how sensory neurons develop in the trunk. They are found in the dorsal root ganglia, which form alongside the spinal cord. They arise from a single embryonic population called neural crest cells during early development and progress through a well-studied path to differentiate as sensory neurons. The situation with the trigeminal nerve is very different however - it is much more complex. The sensory neurons that are concerned with heat, pain and touch are found in the trigeminal ganglion, which does lie alongside the brain, but rather than being derived from a single embryonic population that are derived from 3 distinct populations. Many are derived from thickenings of the embryonic skin, the ophthalmic placode and the maxillomandibular placodes, as well as some from neural crest cells. In stark contrast to what is seen in the trunk, the neurons that transfer information about the spatial position of the jaw are not found in ganglia beside the central nervous system but are rather found within the brain itself. In the trunk, the neurons that monitor the position of the limbs also reside in the dorsal root ganglia.

The aim of this research is to understand the significance of the developmental complexity that we find in the trigeminal system and to test the hypothesis that the embryonic origin of trigeminal sensory neurons matters. Preliminary data suggests that trigeminal sensory neurons send axons to different regions of the head. If this were true for all trigeminal neurons of different origins then this would allow us to demonstrate previously unknown complexity within the trigeminal system. This would have an impact for our understanding of the adult and aging situation. We will determine why the neurons that monitor the positioning of the jaw are sitting within the brain. We will also conduct an in depth comparison between the development of trigeminal and trunk sensory neurons to help us gain insights into the commonalities and differences that exits in the programme that lead to the formation of sensory neurons. Finally, we will also test if the motor neurons that control the movement of the jaw are also important in leading the axons of the sensory neurons that monitor its position to their correct location and how this is achieved

Technical Summary

The sensory neurons that contribute to the trigeminal nerve have a complex developmental history. Those in the trigeminal ganglion derive from three distinct embryonic populations - the ophthalmic placode, the maxillomandibular placode and the cranial neural crest. Furthermore, the trigeminal proprioceptive sensory neurons are born within the dorsal midbrain, and although their embryonic origin is uncertain, evidence suggest that they may be CNS derived. This situation stands in marked contrast to the development of the sensory neurons of the trunk. These are exclusively derived from the neural crest and their development has been well characterised. The significance of the developmental complexity of trigeminal sensory neurons has never been uncovered and it is with this issue that this proposal is concerned. We will use a variety of techniques in both mouse and chick embryos to address this issue These will include fate mapping the different embryonic populations that contribute to the trigeminal using electropration in chick and genetic labelling in mice, misexpression of genes using electroporation in chick and the use of mouse mutants to study the role of motor neurons in directing proprioceptive axons to exit the brain and microarray analysis to explore commonalities and differences between sensory neurons with different embryonic origins.
1 - that sensory neurons of the trigeminal ganglion with distinct developmental origins have distinct central and peripheral projections
2 - that the neurons of the MTN are CNS derived and that their development is intrinsic to neural tissue with a midbrain identity
3 - That sensory neurons of similar modalities with different embryonic origins have distinct developmental paths
4 - that the trigeminal motor axons direct the MTN axons to run in the mandibular ramus

Planned Impact

Our work will have a number of academic impacts. It will advance worldwide academic knowledge in the area of sensory neuron development and vertebrate head development and evolution. Our work will provide an important knowledge base that will allow academics to compare sensory neuronal development in the trunk with that in the trigeminal and to thus identify commonalities and differences that exits in sensory neuronal differentiation. It will also uncover the significance of the developmental complexity of the trigeminal and how that relates generally to head development and evolution and thus inform evolutionary scenarios. It will also have resonance with those in other fields including those interested in the adult and aging nervous system. We predict that the developmental complexity of the trigeminal will underpin different features identified in the adult trigeminal. It will contribute to the health of academic disciplines including developmental biology and evolutionary developmental biology. It will help train highly skilled researchers at the post-doctoral, post-graduate and undergraduate levels through engagement in the project. It will feed into improvements in the teaching and learning of undergraduate science and medical students as it will allow us to use this work as an example of how research is approached and conducted.

Our work will have a number of economic and societal impacts. Through talks to schoolteachers and 6th form students we will work to engage the public how biological research is conducted, the methods used and the types of conclusions that one can arrive at. This will also engage them in think about ethical issues, such as the use of animals in research and the potential benefits of this type of research. Our work may have impact for improving health and well-being. If we find that trigeminal neurons with different embryonic origins project have distinct projections to different areas of the head then this could feed into to our understanding of trigeminal neuropathies. Through our analysis of the commonalities and differences that exist in the development of sensory neurons of different origin in the trigeminal versus those of the trunk we could identify some important specific regulators of sensory neurons development and function which could in turn lead to commercial exploitation.


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Description We have shown that the neurons that help co-rodinate jaw movement have a more complex developmental origin that previously thought. We have been able to identify the pathways that underpin the formation of these different groups of nerve cells. We have defined how these are born and how they initially send out axons to connect with their targets.
Exploitation Route These studies will be useful to the many groups studying the development of sensory neurons as they highlight novel processes involved in the generation of these different populations.
Sectors Education,Pharmaceuticals and Medical Biotechnology

Description We have used the work in general from the lab to engage in outreach activities for school students. This has included hosting students in the lab so that they can get a real feel for a research environment.
First Year Of Impact 2014
Sector Education
Impact Types Societal

Description Analysis of the early development of the mesencephalic trigeminal nucleus 
Organisation Eberhard Karls University of Tubingen
Country Germany 
Sector Academic/University 
PI Contribution Molecular dissection of trigeminal development
Collaborator Contribution Dr Andrea Wizenmann analysed tissue culture explants and electroprated embryos
Impact Papers will be forthcoming
Start Year 2014
Description Outreach Kings college london 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact We run out reach activities through our Museum of Life Sciences here at KCL. This involves local student coming and working through themed workshops. These occur at least once a term.
Year(s) Of Engagement Activity 2012,2013,2014,2015,2016
Description School visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Presentation to year 8 school children to explain what developmental biology is about and why it is important
Year(s) Of Engagement Activity 2015,2016
Description Work experience students 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact We hosted 5 year 12 work experience students and showed then how work in a lab is conducted
Year(s) Of Engagement Activity 2015,2016