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  • Review Article
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Mapping the face in the somatosensory brainstem

Nature Reviews Neuroscience volume 11, pages 252–263 (2010)Cite this article

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Key Points

  • Genetic studies in mice have begun to unravel the molecular mechanisms of somatotopic face map formation in the brainstem. Accumulating evidence indicates that molecular regionalization and positional patterning of the trigeminal ganglion and brainstem target neurons are established by homeodomain transcription factors, the expression of which is induced and maintained by signals derived from the brain and face.

  • Bone morphogenetic protein 4 acts as a putative face-derived retrograde signalling molecule that differentially regulates positionally restricted expression of homeodomain transcription factors in trigeminal ganglion neurons during peripheral axonal targeting. Positional patterning of trigeminal ganglion primary sensory neurons sets the stage for the somatotopy of ophthalmic, maxillary and mandibular central afferents, transforming the spatial distribution of facial sensory receptors into a topographic connectivity map that is in turn conferred to higher brain levels.

  • In the brainstem, the gross somatotopic organization of the rostral principal nucleus (PrV) of the trigeminal nerve is reflected in the spatial segregation of PrV neuron subsets derived from distinct progenitor compartments, or rhombomeres (r). The rhombomere-specific segregation of PrV neurons underlies the parcelling of mandibular and maxillary (whisker-related) segments of the face map in the PrV and the topographic mapping of PrV axons to specific areas of the ventroposteromedial nucleus of the thalamus, where the face map is next conveyed.

  • Homeodomain factor-mediated signals from r2 neuroepithelium during early development restrict the rostral path of the trigeminal tract. In turn, graded homeodomain factor expression in the developing PrV nucleus regulates the topographic branching of mandibular and maxillary trigeminal ganglion afferents in the brainstem, and of PrV efferents to the thalamus.

  • Current evidence indicates the involvement of NMDA (N-methyl D-aspartate) receptors in refining the patterns of dendritic and axonal elements (barrelettes) in the brainstem that replicate the patterned array of whiskers on the snout. However, several questions about the molecular mechanisms underlying the establishment of point-to-point connectivity between the face and the brainstem remain unanswered. For example, what is the role of interactions between neighbouring trigeminal ganglion axons in setting up the preciseconnectivity between the face and the brainstem? What are the molecular characteristics of different classes of cells in the PrV that enable them to form barrelette patterns and convey these patterns to the thalamus?

Abstract

The facial somatosensory map in the cortex is derived from facial representations that are first established at the brainstem level and then serially 'copied' at each stage of the somatosensory pathway. Recent studies have provided insights into the molecular mechanisms involved in the development of somatotopic maps of the face and whiskers in the trigeminal nuclei of the mouse brainstem. This work has revealed that early molecular regionalization and positional patterning of trigeminal ganglion and brainstem target neurons are established by homeodomain transcription factors, the expression of which is induced and maintained by signals from the brain and face. Such position-dependent information is fundamental in transforming the early spatial layout of sensory receptors into a topographic connectivity map that is conferred to higher brain levels.

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Figure 1: Trigeminal circuit and face maps in the mouse brain.
Figure 2: Positional molecular patterning of trigeminal ganglion divisions.
Figure 3: Late expression patterns of homeodomain transcription factors and guidance molecules in the developing TG and PrV.
Figure 4: Relationship between rhombomere progenies and PrV somatotopy.
Figure 5: Phenotypes of the trigeminal system in mutant mice.

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References

  1. Penfield, W. & Boldrey, E. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60, 389–443 (1937).

    Google Scholar 

  2. Belford, G. R. & Killackey, H. P. The development of vibrissae representation in subcortical trigeminal centers of the neonatal rat. J. Comp. Neurol. 188, 63–74 (1979).

    CAS  PubMed  Google Scholar 

  3. Ma, P. M. The barrelettes — architectonic vibrissal representations in the brainstem trigeminal complex of the mouse. I. Normal structural organization. J. Comp. Neurol. 309, 161–199 (1991).

    CAS  PubMed  Google Scholar 

  4. Ma, P. M. Barrelettes — architectonic vibrissal representations in the brainstem trigeminal complex of the mouse. II. Normal post-natal development. J. Comp. Neurol. 327, 376–397 (1993).

    CAS  PubMed  Google Scholar 

  5. Ma, P. M. & Woolsey, T. A. Cytoarchitectonic correlates of the vibrissae in the medullary trigeminal complex of the mouse. Brain Res. 306, 349–374 (1984). This report coined the term 'barrelettes' for the whisker-specific neural modules.

    Google Scholar 

  6. Rebsam, A., Seif, I. & Gaspar, P. Refinement of thalamocortical arbors and emergence of barrel domains in the primary somatosensory cortex: a study of normal and monoamine oxidase A knock-out mice. J. Neurosci. 22, 8541–8552 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Fox, K. Barrel Cortex (Cambridge University Press, New York, 2008).

    Google Scholar 

  8. Grove, E. A. & Fukuchi-Shimogori, T. Generating the cerebral cortical area map. Annu. Rev. Neurosci. 26, 355–380 (2003).

    CAS  PubMed  Google Scholar 

  9. O'Leary, D. D., Chou, S. J. & Sahara, S. Area patterning of the mammalian cortex. Neuron 56, 252–269 (2007).

    CAS  PubMed  Google Scholar 

  10. Sur, M. & Rubenstein, J. L. Patterning and plasticity of the cerebral cortex. Science 310, 805–810 (2005).

    CAS  PubMed  Google Scholar 

  11. Rakic, P. Specification of cerebral cortical areas. Science 241, 170–176 (1988).

    CAS  PubMed  Google Scholar 

  12. Cohen-Tannoudji, M., Babinet, C. & Wassef, M. Early determination of a mouse somatosensory cortex marker. Nature 368, 460–463 (1994).

    CAS  PubMed  Google Scholar 

  13. Erzurumlu, R. S. & Kind, P. C. Neural activity: sculptor of 'barrels' in the neocortex. Trends Neurosci. 24, 589–595 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Lopez-Bendito, G. & Molnar, Z. Thalamocortical development: how are we going to get there? Nature Rev. Neurosci. 4, 276–289 (2003).

    CAS  Google Scholar 

  15. Belford, G. R. & Killackey, H. P. The sensitive period in the development of the trigeminal system of the neonatal rat. J. Comp. Neurol. 193, 335–350 (1980).

    CAS  PubMed  Google Scholar 

  16. Durham, D. & Woolsey, T. A. Effects of neonatal whisker lesions on mouse central trigeminal pathways. J. Comp. Neurol. 223, 424–447 (1984).

    CAS  PubMed  Google Scholar 

  17. Arsenault, D. & Zhang, Z. W. Developmental remodelling of the lemniscal synapse in the ventral basal thalamus of the mouse. J. Physiol. 573, 121–132 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Deschenes, M., Timofeeva, E. & Lavallee, P. The relay of high-frequency sensory signals in the whisker-to-barreloid pathway. J. Neurosci. 23, 6778–6787 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Veinante, P., Jacquin, M. F. & Deschenes, M. Thalamic projections from the whisker-sensitive regions of the spinal trigeminal complex in the rat. J. Comp. Neurol. 420, 233–243 (2000).

    CAS  PubMed  Google Scholar 

  20. Pierret, T., Lavallee, P. & Deschenes, M. Parallel streams for the relay of vibrissal information through thalamic barreloids. J. Neurosci. 20, 7455–7462 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Woolsey, T. A. & Van der Loos, H. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res. 17, 205–242 (1970). This study coined the term 'barrels' for cytoarchitectonic cortical units that correspond to whiskers on the face in a one-to-one fashion.

  22. Van der Loos, H. Barreloids in mouse somatosensory thalamus. Neurosci. Lett. 2, 1–6 (1976). This report describes the cellular organization of the VPM in relation to whisker representation and introduced the term 'barreloids'.

    CAS  PubMed  Google Scholar 

  23. Anderson, D. J. Lineages and transcription factors in the specification of vertebrate primary sensory neurons. Curr. Opin. Neurobiol. 9, 517–524 (1999).

    CAS  PubMed  Google Scholar 

  24. Marmigere, F. & Ernfors, P. Specification and connectivity of neuronal subtypes in the sensory lineage. Nature Rev. Neurosci. 8, 114–127 (2007).

    CAS  Google Scholar 

  25. Kiecker, C. & Lumsden, A. Compartments and their boundaries in vertebrate brain development. Nature Rev. Neurosci. 6, 553–564 (2005).

    CAS  Google Scholar 

  26. Ayer-Le Lievre, C. S. & Le Douarin, N. M. The early development of cranial sensory ganglia and the potentialities of their component cells studied in quail-chick chimeras. Dev. Biol. 94, 291–310 (1982).

    CAS  PubMed  Google Scholar 

  27. Noden, D. M. Somatotopic organization of the embryonic chick trigeminal ganglion. J. Comp. Neurol. 190, 429–444 (1980).

    CAS  PubMed  Google Scholar 

  28. D' Amico-Martel, A. & Noden, D. M. Contributions of placodal and neural crest cells to avian cranial peripheral ganglia. Am. J. Anat. 166, 445–468 (1983).

    PubMed  Google Scholar 

  29. Couly, G. & Le Douarin, N. M. Head morphogenesis in embryonic avian chimeras: evidence for a segmental pattern in the ectoderm corresponding to the neuromeres. Development 108, 543–558 (1990).

    CAS  PubMed  Google Scholar 

  30. Lumsden, A., Sprawson, N. & Graham, A. Segmental origin and migration of neural crest cells in the hindbrain region of the chick embryo. Development 113, 1281–1291 (1991).

    CAS  PubMed  Google Scholar 

  31. Serbedzija, G. N., Bronner-Fraser, M. & Fraser, S. E. Vital dye analysis of cranial neural crest cell migration in the mouse embryo. Development 116, 297–307 (1992).

    CAS  PubMed  Google Scholar 

  32. Begbie, J., Ballivet, M. & Graham, A. Early steps in the production of sensory neurons by the neurogenic placodes. Mol. Cell Neurosci. 21, 502–511 (2002).

    CAS  PubMed  Google Scholar 

  33. Santagati, F. & Rijli, F. M. Cranial neural crest and the building of the vertebrate head. Nature Rev. Neurosci. 4, 806–818 (2003).

    CAS  Google Scholar 

  34. Baker, C. V. & Bronner-Fraser, M. Vertebrate cranial placodes I. Embryonic induction. Dev. Biol. 232, 1–61 (2001).

    CAS  PubMed  Google Scholar 

  35. Streit, A. Early development of the cranial sensory nervous system: from a common field to individual placodes. Dev. Biol. 276, 1–15 (2004).

    CAS  PubMed  Google Scholar 

  36. Schlosser, G. Induction and specification of cranial placodes. Dev. Biol. 294, 303–351 (2006).

    CAS  PubMed  Google Scholar 

  37. Shiau, C. E., Lwigale, P. Y., Das, R. M., Wilson, S. A. & Bronner-Fraser, M. Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion. Nature Neurosci. 11, 269–276 (2008).

    CAS  PubMed  Google Scholar 

  38. Stark, M. R., Sechrist, J., Bronner-Fraser, M. & Marcelle, C. Neural tube-ectoderm interactions are required for trigeminal placode formation. Development 124, 4287–4295 (1997).

    CAS  PubMed  Google Scholar 

  39. Baker, C. V., Stark, M. R., Marcelle, C. & Bronner-Fraser, M. Competence, specification and induction of Pax-3 in the trigeminal placode. Development 126, 147–156 (1999).

    CAS  PubMed  Google Scholar 

  40. Xu, H., Dude, C. M. & Baker, C. V. Fine-grained fate maps for the ophthalmic and maxillomandibular trigeminal placodes in the chick embryo. Dev. Biol. 317, 174–186 (2008).

    CAS  PubMed  Google Scholar 

  41. Knaut, H., Blader, P., Strähle, U. & Schier, A. F. Assembly of trigeminal sensory ganglia by chemokine signaling. Neuron 47, 653–666 (2005).

    CAS  PubMed  Google Scholar 

  42. Kerstetter, A. E., Azodi, E., Marss, J. A. & Liu, Q. Cadherin-2 function in the cranial ganglia and lateral line system of developing zebrafish. Dev. Dyn. 230, 137–143 (2004).

    CAS  PubMed  Google Scholar 

  43. Shiau, C. E. & Bronner-Fraser, M. N-cadherin acts in concert with Slit1-Robo2 signaling in regulating aggregation of placode-derived cranial sensory neurons. Development 136, 4155–4164 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Hodge, L. K. et al. Retrograde BMP signaling regulates trigeminal sensory neuron identities and the formation of precise face maps. Neuron 55, 572–586 (2007). The authors identify BMP4 as a face-derived retrograde signaling molecule that differentially regulates positionally restricted expression of homeodomain transcription factors in TG neurons.

    CAS  PubMed  Google Scholar 

  45. McCabe, K. L. & Bronner-Fraser, M. Essential role for PDGF signaling in ophthalmic trigeminal placode induction. Development 135, 1863–1874 (2008).

    CAS  PubMed  Google Scholar 

  46. Wurst, W. & Bally-Cuif, L. Neural plate patterning: upstream and downstream of the isthmic organizer. Nature Rev. Neurosci. 2, 99–108 (2001).

    CAS  Google Scholar 

  47. Canning, C. A., Lee, L., Luo, S. X., Graham, A. & Jones, C. M. Neural tube derived Wnt signals cooperate with FGF signaling in the formation and differentiation of the trigeminal placodes. Neural Dev. 3, 35 (2008).

    PubMed  PubMed Central  Google Scholar 

  48. Irving, C. & Mason, I. Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression. Development 127, 177–186 (2000).

    CAS  PubMed  Google Scholar 

  49. Trainor, P. A., Ariza-McNaughton, L. & Krumlauf, R. Role of the isthmus and FGFs in resolving the paradox of neural crest plasticity and prepatterning. Science 295, 1288–1291 (2002).

    CAS  PubMed  Google Scholar 

  50. Fukuchi-Shimogori, T. & Grove, E. A. Neocortex patterning by the secreted signaling molecule FGF8. Science 294, 1071–1074 (2001).

    CAS  PubMed  Google Scholar 

  51. Lumsden, A. G. & Davies, A. M. Earliest sensory nerve fibres are guided to peripheral targets by attractants other than nerve growth factor. Nature 306, 786–788 (1983).

    CAS  PubMed  Google Scholar 

  52. Lumsden, A. G. & Davies, A. M. Chemotropic effect of specific target epithelium in the developing mammalian nervous system. Nature 323, 538–539 (1986).

    CAS  PubMed  Google Scholar 

  53. O'Connor, R. & Tessier-Lavigne, M. Identification of maxillary factor, a maxillary process-derived chemoattractant for developing trigeminal sensory axons. Neuron 24, 165–178 (1999). This study identified the putative maxillary factor that attracts the earliest trigeminal peripheral axons as a combination of NTF3 and BDNF, for which a neurotrophic role was shown.

    CAS  PubMed  Google Scholar 

  54. Erzurumlu, R. S., Chen, Z. F. & Jacquin, M. F. Molecular determinants of the face map development in the trigeminal brainstem. Anat. Rec. A Discov. Mol. Cell Evol. Biol. 288, 121–134 (2006).

    PubMed  PubMed Central  Google Scholar 

  55. Kobayashi, H., Koppel, A. M., Luo, Y. & Raper, J. A. A role for collapsin-1 in olfactory and cranial sensory axon guidance. J. Neurosci. 17, 8339–8352 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kitsukawa, T. et al. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 19, 995–1005 (1997).

    CAS  PubMed  Google Scholar 

  57. Ulupinar, E., Datwani, A., Behar, O., Fujisawa, H. & Erzurumlu, R. Role of semaphorin III in the developing rodent trigeminal system. Mol. Cell Neurosci. 13, 281–292 (1999). Pathfinding defects in mice lacking SEM3A illustrate the role of this repulsive axon guidance molecule in restricing peripheral and central projections of trigeminal ganglion axons.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. White, F. A. & Behar, O. The development and subsequent elimination of aberrant peripheral axon projections in Semaphorin3A null mutant mice. Dev. Biol. 225, 79–86 (2000).

    CAS  PubMed  Google Scholar 

  59. Ozdinler, P. H. & Erzurumlu, R. S. Slit2, a branching-arborization factor for sensory axons in the mammalian CNS. J. Neurosci. 22, 4540–4549 (2002). Axon branching effects of SLIT2 are demonstrated in organotypic wholemount cultures of the trigeminal ganglion brainstem preparations from rat embryos.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Ma, L. & Tessier-Lavigne, M. Dual branch-promoting and branch-repelling actions of Slit/Robo signaling on peripheral and central branches of developing sensory axons. J. Neurosci. 27, 6843–6851 (2007). Defects in peripheral projections of the ophthalmic branch of the trigeminal nerve are shown in multiple Slit-deficient mouse embryos.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Guha, U. et al. Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo. Development 131, 1175–1186 (2004).

    CAS  PubMed  Google Scholar 

  62. Graham, A., Francis-West, P., Brickell, P. & Lumsden, A. The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest. Nature 372, 684–686 (1994).

    CAS  PubMed  Google Scholar 

  63. Nie, X., Luukko, K. & Kettunen, P. BMP signalling in craniofacial development. Int. J. Dev. Biol. 50, 511–521 (2006).

    CAS  PubMed  Google Scholar 

  64. Abzhanov, A., Protas, M., Grant, B. R., Grant, P. R. & Tabin, C. J. Bmp4 and morphological variation of beaks in Darwin's finches. Science 305, 1462–1465 (2004).

    CAS  PubMed  Google Scholar 

  65. Wu, P., Jiang, T. X., Suksaweang, S., Widelitz, R. B. & Chuong, C. M. Molecular shaping of the beak. Science 305, 1465–1466 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Erzurumlu, R. S. & Ebner, F. F. Maintenance of discrete somatosensory maps in subcortical relay nuclei is dependent on an intact sensory cortex. Brain Res. Dev. Brain Res. 44, 302–308 (1988).

    CAS  PubMed  Google Scholar 

  67. Killackey, H. P. & Fleming, K. The role of the principal sensory nucleus in central trigeminal pattern formation. Brain Res. 354, 141–145 (1985).

    CAS  PubMed  Google Scholar 

  68. Erzurumlu, R. S. & Jhaveri, S. Trigeminal ganglion cell processes are spatially ordered prior to the differentiation of the vibrissa pad. J. Neurosci. 12, 3946–3955 (1992). The first application of carbocyanine labelling to developing trigeminal axons confirmed the topographic order of the trigeminal projections from the periphery to the brainstem and showed that trigeminothalamic projections from the PrV alone are responsible for whisker-specific pattern formation in the thalamus.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Erzurumlu, R. S. & Jhaveri, S. Thalamic axons confer a blueprint of the sensory periphery onto the developing rat somatosensory cortex. Brain Res. Dev. Brain Res. 56, 229–234 (1990).

    CAS  PubMed  Google Scholar 

  70. Erzurumlu, R. S. & Jhaveri, S. Emergence of connectivity in the embryonic rat parietal cortex. Cereb. Cortex 2, 336–352 (1992).

    CAS  PubMed  Google Scholar 

  71. Senft, S. L. & Woolsey, T. A. Computer-aided analyses of thalamocortical afferent ingrowth. Cereb. Cortex 1, 336–347 (1991).

    CAS  PubMed  Google Scholar 

  72. Oury, F. et al. Hoxa2- and rhombomere-dependent development of the mouse facial somatosensory map. Science 313, 1408–1413 (2006). This study mapped the rhombomeric origin and Hoxa2 -dependent patterning of the mouse PrV and its whisker and lower-jaw representations.

    CAS  PubMed  Google Scholar 

  73. Marin, F. & Puelles, L. Morphological fate of rhombomeres in quail/chick chimeras: a segmental analysis of hindbrain nuclei. Eur. J. Neurosci. 7, 1714–1738 (1995).

    CAS  PubMed  Google Scholar 

  74. Lumsden, A. The cellular basis of segmentation in the developing hindbrain. Trends Neurosci. 13, 329–335 (1990).

    CAS  PubMed  Google Scholar 

  75. Carpenter, E. M., Goddard, J. M., Chisaka, O., Manley, N. R. & Capecchi, M. R. Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain. Development 118, 1063–1075 (1993).

    CAS  PubMed  Google Scholar 

  76. Clarke, J. D. & Lumsden, A. Segmental repetition of neuronal phenotype sets in the chick embryo hindbrain. Development 118, 151–162 (1993).

    CAS  PubMed  Google Scholar 

  77. Cordes, S. P. Molecular genetics of cranial nerve development in mouse. Nature Rev. Neurosci. 2, 611–623 (2001).

    CAS  Google Scholar 

  78. Farago, A. F., Awatramani, R. B. & Dymecki, S. M. Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps. Neuron 50, 205–218 (2006).

    CAS  PubMed  Google Scholar 

  79. Fraser, S., Keynes, R. & Lumsden, A. Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions. Nature 344, 431–435 (1990).

    CAS  PubMed  Google Scholar 

  80. Lumsden, A. & Keynes, R. Segmental patterns of neuronal development in the chick hindbrain. Nature 337, 424–428 (1989).

    CAS  PubMed  Google Scholar 

  81. Metcalfe, W. K., Mendelson, B. & Kimmel, C. B. Segmental homologies among reticulospinal neurons in the hindbrain of the zebrafish larva. J. Comp. Neurol. 251, 147–159 (1986).

    CAS  PubMed  Google Scholar 

  82. Pasqualetti, M., Diaz, C., Renaud, J. S., Rijli, F. M. & Glover, J. C. Fate-mapping the mammalian hindbrain: segmental origins of vestibular projection neurons assessed using rhombomere-specific Hoxa2 enhancer elements in the mouse embryo. J. Neurosci. 27, 9670–9681 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Wingate, R. J. & Lumsden, A. Persistence of rhombomeric organisation in the postsegmental hindbrain. Development 122, 2143–2152 (1996).

    CAS  PubMed  Google Scholar 

  84. Wizenmann, A. & Lumsden, A. Segregation of rhombomeres by differential chemoaffinity. Mol. Cell Neurosci. 9, 448–459 (1997).

    CAS  PubMed  Google Scholar 

  85. Erzurumlu, R. S. & Killackey, H. P. Development of order in the rat trigeminal system. J. Comp. Neurol. 213, 365–380 (1983). The first study depicting topographic order in the infraorbital nerve, the trigeminal ganglion and brainstem projections in rat embryos.

    CAS  PubMed  Google Scholar 

  86. al-Ghoul, W. M. & Miller, M. W. Orderly migration of neurons to the principal sensory nucleus of the trigeminal nerve of the rat. J. Comp. Neurol. 330, 464–475 (1993).

    CAS  PubMed  Google Scholar 

  87. Altman, J. & Bayer, S. A. Development of the brain stem in the rat. IV. Thymidine-radiographic study of the time of origin of neurons in the pontine region. J. Comp. Neurol. 194, 905–929 (1980).

    CAS  PubMed  Google Scholar 

  88. Nornes, H. O. & Morita, M. Time of origin of the neuronsin the caudal brain stem of the rat. An autoradiographic study. Dev. Neurosci. 2, 101–114 (1979).

    Google Scholar 

  89. Miller, M. W. & Muller, S. J. Structure and histogenesis of the principal sensory nucleus of the trigeminal nerve: effect of prenatal exposure to ethanol. J. Comp. Neurol. 282, 570–580 (1989).

    CAS  PubMed  Google Scholar 

  90. Ding, Y. Q., Yin, J., Xu, H. M., Jacquin, M. F. & Chen, Z. F. Formation of whisker-related principal sensory nucleus-based lemniscal pathway requires a paired homeodomain transcription factor, Drg11. J. Neurosci. 23, 7246–7254 (2003). The first study to show the involvement of a homeodomain transcription factor, DRG11, in PrV development.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Belford, G. R. & Killackey, H. P. Vibrissae representation in subcortical trigeminal centers of the neonatal rat. J. Comp. Neurol. 183, 305–321 (1979). The first study depicting the development of pattern formation along the subcortical trigeminal centers of postnatal rats.

    CAS  PubMed  Google Scholar 

  92. Leamey, C. A. & Ho, S. M. Afferent arrival and onset of functional activity in the trigeminothalamic pathway of the rat. Brain Res. Dev. Brain Res. 105, 195–207 (1998). These authors show that rat trigeminothalamic fibres are synaptically active as soon as they reach the thalamus.

    CAS  PubMed  Google Scholar 

  93. Lim, Y. & Golden, J. A. Patterning the developing diencephalon. Brain Res. Rev. 53, 17–26 (2007).

    PubMed  Google Scholar 

  94. Altman, J. & Bayer, S. A. Development of the rat thalamus: I. Mosaic organization of the thalamic neuroepithelium. J. Comp. Neurol. 275, 346–377 (1988).

    CAS  PubMed  Google Scholar 

  95. Altman, J. & Bayer, S. A. Development of the rat thalamus: IV. The intermediate lobule of the thalamic neuroepithelium, and the time and site of origin and settling pattern of neurons of the ventral nuclear complex. J. Comp. Neurol. 284, 534–566 (1989).

    CAS  PubMed  Google Scholar 

  96. Deschenes, M., Timofeeva, E., Lavallee, P. & Dufresne, C. The vibrissal system as a model of thalamic operations. Prog. Brain Res. 149, 31–40 (2005).

    PubMed  Google Scholar 

  97. Sherman, S. M. & Guillery, R. W. Functional organization of thalamocortical relays. J. Neurophysiol. 76, 1367–1395 (1996).

    CAS  PubMed  Google Scholar 

  98. Trageser, J. C. et al. State-dependent gating of sensory inputs by zona incerta. J. Neurophysiol. 96, 1456–1463 (2006).

    PubMed  Google Scholar 

  99. Krumlauf, R. Hox Genes and patterning in mammals. Annu. Rev. Cell Dev. Biol. 45, 431–456 (2009).

    Google Scholar 

  100. Lumsden, A. & Krumlauf, R. Patterning the vertebrate neuraxis. Science 274, 1109–1115 (1996).

    CAS  PubMed  Google Scholar 

  101. Narita, Y. & Rijli, F. M. Hox genes in neural patterning and circuit formation in the mouse hindbrain. Curr. Top. Dev. Biol. 88, 139–167 (2009).

    CAS  PubMed  Google Scholar 

  102. Davenne, M. et al. Hoxa2 and Hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain. Neuron 22, 677–691 (1999).

    CAS  PubMed  Google Scholar 

  103. Gaufo, G. O., Flodby, P. & Capecchi, M. R. Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Development 127, 5343–5354 (2000).

    CAS  PubMed  Google Scholar 

  104. Gaufo, G. O., Wu, S. & Capecchi, M. R. Contribution of Hox genes to the diversity of the hindbrain sensory system. Development 131, 1259–1266 (2004).

    CAS  PubMed  Google Scholar 

  105. Geisen, M. J. et al. Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling. PLoS Biol. 6, e142 (2008).

    PubMed  PubMed Central  Google Scholar 

  106. Dasen, J. S. & Jessell, T. M. Hox networks and the origins of motor neuron diversity. Curr. Top. Dev. Biol. 88, 169–200 (2009).

    CAS  PubMed  Google Scholar 

  107. Dasen, J. S., Liu, J. P. & Jessell, T. M. Motor neuron columnar fate imposed by sequential phases of Hox-c activity. Nature 425, 926–933 (2003).

    CAS  PubMed  Google Scholar 

  108. Dasen, J. S., Tice, B. C., Brenner-Morton, S. & Jessell, T. M. A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity. Cell 123, 477–491 (2005).

    CAS  PubMed  Google Scholar 

  109. Hunt, P. et al. A distinct Hox code for the branchial region of the vertebrate head. Nature 353, 861–864 (1991).

    CAS  PubMed  Google Scholar 

  110. Krumlauf, R. Hox genes and pattern formation in the branchial region of the vertebrate head. Trends Genet. 9, 106–112 (1993).

    CAS  PubMed  Google Scholar 

  111. Prince, V. & Lumsden, A. Hoxa-2 expression in normal and transposed rhombomeres: independent regulation in the neural tube and neural crest. Development 120, 911–923 (1994).

    CAS  PubMed  Google Scholar 

  112. Tan, D. P. et al. Murine Hox-1.11 homeobox gene structure and expression. Proc. Natl Acad. Sci. USA 89, 6280–6284 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Erzurumlu, R. S., Jhaveri, S., Takahashi, H. & McKay, R. D. Target-derived influences on axon growth modes in cultures of trigeminal neurons. Proc. Natl Acad. Sci. USA 90, 7235–7239 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Vanderhaeghen, P. et al. A mapping label required for normal scale of body representation in the cortex. Nature Neurosci. 3, 358–365 (2000).

    CAS  PubMed  Google Scholar 

  115. Jacquin, M. F. et al. In DRG11 knock-out mice, trigeminal cell death is extensive and does not account for failed brainstem patterning. J. Neurosci. 28, 3577–3585 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Rebelo, S. et al. DRG11 immunohistochemical expression during embryonic development in the mouse. Dev. Dyn. 236, 2653–2660 (2007).

    CAS  PubMed  Google Scholar 

  117. Logan, C., Wingate, R. J., McKay, I. J. & Lumsden, A. Tlx-1 and Tlx-3 homeobox gene expression in cranial sensory ganglia and hindbrain of the chick embryo: markers of patterned connectivity. J. Neurosci. 18, 5389–5402 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Qian, Y., Shirasawa, S., Chen, C. L., Cheng, L. & Ma, Q. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1. Genes Dev. 16, 1220–1233 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Dai, J. X., Hu, Z. L., Shi, M., Guo, C. & Ding, Y. Q. Postnatal ontogeny of the transcription factor Lmx1b in the mouse central nervous system. J. Comp. Neurol. 509, 341–355 (2008).

    CAS  PubMed  Google Scholar 

  120. Cheng, L. et al. Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nature Neurosci. 7, 510–517 (2004).

    CAS  PubMed  Google Scholar 

  121. Shigetani, Y., Nobusada, Y. & Kuratani, S. Ectodermally derived FGF8 defines the maxillomandibular region in the early chick embryo: epithelial-mesenchymal interactions in the specification of the craniofacial ectomesenchyme. Dev. Biol. 228, 73–85 (2000).

    CAS  PubMed  Google Scholar 

  122. Shigetani, Y. et al. Heterotopic shift of epithelial-mesenchymal interactions in vertebrate jaw evolution. Science 296, 1316–1319 (2002).

    CAS  PubMed  Google Scholar 

  123. Shigetani, Y., Sugahara, F. & Kuratani, S. A new evolutionary scenario for the vertebrate jaw. Bioessays 27, 331–338 (2005).

    CAS  PubMed  Google Scholar 

  124. Andres, F. L. & Van der Loos, H. Whisker patterns form in cultured non-innervated muzzle skin from mouse embryos. Neurosci. Lett. 30, 37–41 (1982).

    CAS  PubMed  Google Scholar 

  125. Sagasti, A., Guido, M. R., Raible, D. W. & Schier, A. F. Repulsive interactions shape the morphologies and functional arrangement of zebrafish peripheral sensory arbors. Curr. Biol. 15, 804–814 (2005).

    CAS  PubMed  Google Scholar 

  126. Kutsuwada, T. et al. Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice. Neuron 16, 333–344 (1996).

    CAS  PubMed  Google Scholar 

  127. Li, Y., Erzurumlu, R. S., Chen, C., Jhaveri, S. Tonegawa, S. Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76, 427–437 (1994). This study is the first demonstration that NMDAR function is essential in patterning of the trigeminal afferents in the PrV but not in their topographic ordering.

    CAS  PubMed  Google Scholar 

  128. Iwasato, T. et al. NMDA receptor-dependent refinement of somatotopic maps. Neuron 19, 1201–1210 (1997).

    CAS  PubMed  Google Scholar 

  129. Lee, L. J., Lo, F. S. & Erzurumlu, R. S. NMDA receptor-dependent regulation of axonal and dendritic branching. J. Neurosci. 25, 2304–2311 (2005). This study describes the role of NMDARs in trigeminal axonal branching and dendritic orientation of PrV barrelette cells in Nmdar mutant mice.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Stainier, D. Y. & Gilbert, W. Pioneer neurons in the mouse trigeminal sensory system. Proc. Natl Acad. Sci. USA 87, 923–927 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Stainier, D. Y. & Gilbert, W. Neuronal differentiation and maturation in the mouse trigeminal sensory system, in vivo and in vitro. J. Comp. Neurol. 311, 300–312 (1991).

    CAS  PubMed  Google Scholar 

  132. Waite, P. M., Ho, S. M. & Henderson, T. A. Afferent ingrowth and onset of activity in the rat trigeminal nucleus. Eur. J. Neurosci. 12, 2781–2792 (2000). This study showed that embryonic trigeminal axons are synaptically active as they enter the brainstem trigeminal nuclei.

    CAS  PubMed  Google Scholar 

  133. Chiaia, N. L. et al. Evidence for prenatal competition among the central arbors of trigeminal primary afferent neurons. J. Neurosci. 12, 62–76 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Hayashi, H. Distributions of vibrissae afferent fiber collaterals in the trigeminal nuclei as revealed by intra-axonal injection of horseradish peroxidase. Brain Res. 183, 442–446 (1980).

    CAS  PubMed  Google Scholar 

  135. Henderson, T. A. & Jacquin, M. F. What Makes Subcortical Barrels? 123–187 (Plenum,New York, 1995).

    Google Scholar 

  136. Lo, F. S., Guido, W. & Erzurumlu, R. S. Electrophysiological properties and synaptic responses of cells in the trigeminal principal sensory nucleus of postnatal rats. J. Neurophysiol. 82, 2765–2775 (1999). Membrane properties and synaptic responses of PrV cells in neonatal rats are described.

    CAS  PubMed  Google Scholar 

  137. Rudhard, Y. et al. Absence of whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling. J. Neurosci. 23, 2323–2332 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Single, F. N. et al. Dysfunctions in mice by NMDA receptor point mutations NR1 (N598Q) and NR1 (N598R). J. Neurosci. 20, 2558–2566 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Taniguchi, M. et al. Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 19, 519–530 (1997).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the members of the F.M.R. laboratory for discussion and comments on an earlier version of the manuscript. Work in the R.S.E. laboratory is supported by funding from NIH/NINDS (RO1 NS037070, RO1 NS039050 and PO1 NS049048-23000209). Work in the F.M.R. laboratory is supported by the Swiss National Science Foundation and the Novartis Research Foundation.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Maryland, School of Medicine, Baltimore, 21201, Maryland, USA

    Reha S. Erzurumlu

  2. Department of Science, Graduate School of Science and Engineering, Ehime University, Bunkyo-cho, Matsuyama, 7908577, Ehime, Japan

    Yasunori Murakami

  3. Friedrich Miescher Institute for Biomedical Research, Maulberstrasse 66, Basel, 4058, Switzerland

    Filippo M. Rijli

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  1. Reha S. Erzurumlu
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  3. Filippo M. Rijli
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Glossary

Homunculus

Literally 'little man', it refers to the somatosensory and motor body maps in the human brain.

Critical period

A finite but modifiable developmental time window during which sensory experience-mediated input provides information that is essential for normal maturation of sensory circuits.

Epigenetics

Changes in phenotype or gene expression caused by mechanisms other than genetic factors.

Neural crest

Groups of cells that migrate from the neural tube to the periphery, where they give rise to a wide range of cell types.

Rhombomeres

Neuroepithelial segments found transiently in the embryonic hindbrain that adopt distinct molecular and cellular properties, restrictions in cell mixing and ordered domains of gene expression.

Neuroectoderm

Part of the ectoderm that gives rise to the neural crest and neural tube.

Ventricular zone

The proliferative region of the mammalian brain adjacent to the brain ventricles that gives rise to neurons and glia.

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Erzurumlu, R., Murakami, Y. & Rijli, F. Mapping the face in the somatosensory brainstem. Nat Rev Neurosci 11, 252–263 (2010). https://doi.org/10.1038/nrn2804

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