1932

Abstract

Control of movement is a fundamental and complex task of the vertebrate nervous system, which relies on communication between circuits distributed throughout the brain and spinal cord. Many of the networks essential for the execution of basic locomotor behaviors are composed of discrete neuronal populations residing within the spinal cord. The organization and connectivity of these circuits is established through programs that generate functionally diverse neuronal subtypes, each contributing to a specific facet of motor output. Significant progress has been made in deciphering how neuronal subtypes are specified and in delineating the guidance and synaptic specificity determinants at the core of motor circuit assembly. Recent studies have shed light on the basic principles linking locomotor circuit connectivity with function, and they are beginning to reveal how more sophisticated motor behaviors are encoded. In this review, we discuss the impact of developmental programs in specifying motor behaviors governed by spinal circuits.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-100814-125155
2015-11-13
2024-05-18
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/31/1/annurev-cellbio-100814-125155.html?itemId=/content/journals/10.1146/annurev-cellbio-100814-125155&mimeType=html&fmt=ahah

Literature Cited

  1. Abraira VE, Ginty DD. 2013. The sensory neurons of touch. Neuron 79:618–39 [Google Scholar]
  2. Alexander T, Nolte C, Krumlauf R. 2009. Hox genes and segmentation of the hindbrain and axial skeleton. Annu. Rev. Cell Dev. Biol. 25:431–56 [Google Scholar]
  3. Alstermark B, Isa T, Ohki Y, Saito Y. 1999. Disynaptic pyramidal excitation in forelimb motoneurons mediated via C3-C4 propriospinal neurons in the Macaca fuscata. J. Neurophysiol. 82:3580–85 [Google Scholar]
  4. Alvarez FJ, Jonas PC, Sapir T, Hartley R, Berrocal MC. et al. 2005. Postnatal phenotype and localization of spinal cord V1 derived interneurons. J. Comp. Neurol. 493:177–92 [Google Scholar]
  5. Ampatzis K, Song JR, Ausborn J, El Manira A. 2014. Separate microcircuit modules of distinct V2a interneurons and motoneurons control the speed of locomotion. Neuron 83:934–43 [Google Scholar]
  6. Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D. et al. 2012. Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Nature 488:642–46 [Google Scholar]
  7. Arber S. 2012. Motor circuits in action: specification, connectivity, and function. Neuron 74:975–89 [Google Scholar]
  8. Arber S, Ladle DR, Lin JH, Frank E, Jessell TM. 2000. ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell 101:485–98 [Google Scholar]
  9. Augsburger A, Schuchardt A, Hoskins S, Dodd J, Butler S. 1999. BMPs as mediators of roof plate repulsion of commissural neurons. Neuron 24:127–41 [Google Scholar]
  10. Azim E, Jiang J, Alstermark B, Jessell TM. 2014. Skilled reaching relies on a V2a propriospinal internal copy circuit. Nature 508:357–63 [Google Scholar]
  11. Bagnall MW, McLean DL. 2014. Modular organization of axial microcircuits in zebrafish. Science 343:197–200 [Google Scholar]
  12. Balaskas N, Ribeiro A, Panovska J, Dessaud E, Sasai N. et al. 2012. Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube. Cell 148:273–84 [Google Scholar]
  13. Bekoff A. 2001. Spontaneous embryonic motility: an enduring legacy. Int. J. Dev. Neurosci. 19:155–60 [Google Scholar]
  14. Bel-Vialar S, Itasaki N, Krumlauf R. 2002. Initiating Hox gene expression: In the early chick neural tube differential sensitivity to FGF and RA signaling subdivides the HoxB genes in two distinct groups. Development 129:5103–15 [Google Scholar]
  15. Bello SM, Millo H, Rajebhosale M, Price SR. 2012. Catenin-dependent cadherin function drives divisional segregation of spinal motor neurons. J. Neurosci. 32:490–505 [Google Scholar]
  16. Bonanomi D, Chivatakarn O, Bai G, Abdesselem H, Lettieri K. et al. 2012. Ret is a multifunctional coreceptor that integrates diffusible- and contact-axon guidance signals. Cell 148:568–82 [Google Scholar]
  17. Bonanomi D, Pfaff SL. 2010. Motor axon pathfinding. Cold Spring Harb. Perspect. Biol. 2:a001735 [Google Scholar]
  18. Borgius L, Nishimaru H, Caldeira V, Kunugise Y, Low P. et al. 2014. Spinal glutamatergic neurons defined by EphA4 signaling are essential components of normal locomotor circuits. J. Neurosci. 34:3841–53 [Google Scholar]
  19. Bosco G, Poppele RE. 2001. Proprioception from a spinocerebellar perspective. Physiol. Rev. 81:539–68 [Google Scholar]
  20. Bourane S, Grossmann KS, Britz O, Dalet A, Del Barrio MG. et al. 2015. Identification of a spinal circuit for light touch and fine motor control. Cell 160:503–15 [Google Scholar]
  21. Bourikas D, Pekarik V, Baeriswyl T, Grunditz A, Sadhu R. et al. 2005. Sonic hedgehog guides commissural axons along the longitudinal axis of the spinal cord. Nat. Neurosci. 8:297–304 [Google Scholar]
  22. Briscoe J, Pierani A, Jessell TM, Ericson J. 2000. A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101:435–45 [Google Scholar]
  23. Brown AG. 1981. Organization in the Spinal Cord: the Anatomy and Physiology of Identified Neurones Berlin/New York: Springer
  24. Brown AG, Fyffe RE. 1978. The morphology of group Ia afferent fibre collaterals in the spinal cord of the cat. J. Physiol. 274:111–27 [Google Scholar]
  25. Brown AG, Fyffe RE. 1979. The morphology of group Ib afferent fibre collaterals in the spinal cord of the cat. J. Physiol. 296:215–26 [Google Scholar]
  26. Bui TV, Akay T, Loubani O, Hnasko TS, Jessell TM, Brownstone RM. 2013. Circuits for grasping: Spinal dI3 interneurons mediate cutaneous control of motor behavior. Neuron 78:191–204 [Google Scholar]
  27. Burke RE, Glenn LL. 1996. Horseradish peroxidase study of the spatial and electrotonic distribution of group Ia synapses on type-identified ankle extensor motoneurons in the cat. J. Comp. Neurol. 372:465–85 [Google Scholar]
  28. Butler SJ, Dodd J. 2003. A role for BMP heterodimers in roof plate–mediated repulsion of commissural axons. Neuron 38:389–401 [Google Scholar]
  29. Butler SJ, Tear G. 2007. Getting axons onto the right path: the role of transcription factors in axon guidance. Development 134:439–48 [Google Scholar]
  30. Butt SJ, Lundfald L, Kiehn O. 2005. EphA4 defines a class of excitatory locomotor-related interneurons. PNAS 102:14098–103 [Google Scholar]
  31. Charoy C, Nawabi H, Reynaud F, Derrington E, Bozon M. et al. 2012. gdnf activates midline repulsion by Semaphorin3B via NCAM during commissural axon guidance. Neuron 75:1051–66 [Google Scholar]
  32. Charron F, Stein E, Jeong J, McMahon AP, Tessier-Lavigne M. 2003. The morphogen Sonic Hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113:11–23 [Google Scholar]
  33. Chen Z, Gore BB, Long H, Ma L, Tessier-Lavigne M. 2008. Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion. Neuron 58:325–32 [Google Scholar]
  34. Cowley KC, Schmidt BJ. 1995. Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord. J. Neurophysiol. 74:1109–17 [Google Scholar]
  35. Cowley KC, Schmidt BJ. 1997. Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord. J. Neurophysiol. 77:247–59 [Google Scholar]
  36. Crapse TB, Sommer MA. 2008. Corollary discharge across the animal kingdom. Nat. Rev. Neurosci. 9:587–600 [Google Scholar]
  37. Crone SA, Quinlan KA, Zagoraiou L, Droho S, Restrepo CE. et al. 2008. Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron 60:70–83 [Google Scholar]
  38. Crone SA, Zhong G, Harris-Warrick R, Sharma K. 2009. In mice lacking V2a interneurons, gait depends on speed of locomotion. J. Neurosci. 29:7098–109 [Google Scholar]
  39. Dasen JS. 2009. Transcriptional networks in the early development of sensory-motor circuits. Curr. Top. Dev. Biol. 87:119–48 [Google Scholar]
  40. Dasen JS, De Camilli A, Wang B, Tucker PW, Jessell TM. 2008. Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell 134:304–16 [Google Scholar]
  41. Dasen JS, Jessell TM. 2009. Hox networks and the origins of motor neuron diversity. Curr. Top. Dev. Biol. 88:169–200 [Google Scholar]
  42. Dasen JS, Liu JP, Jessell TM. 2003. Motor neuron columnar fate imposed by sequential phases of Hox-c activity. Nature 425:926–33 [Google Scholar]
  43. Dasen JS, Tice BC, Brenner-Morton S, Jessell TM. 2005. A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity. Cell 123:477–91 [Google Scholar]
  44. de Nooij JC, Doobar S, Jessell TM. 2013. Etv1 inactivation reveals proprioceptor subclasses that reflect the level of NT3 expression in muscle targets. Neuron 77:1055–68 [Google Scholar]
  45. Delloye-Bourgeois C, Jacquier A, Charoy C, Reynaud F, Nawabi H. et al. 2015. PlexinA1 is a new Slit receptor and mediates axon guidance function of Slit C-terminal fragments. Nat. Neurosci. 18:36–45 [Google Scholar]
  46. Demireva EY, Shapiro LS, Jessell TM, Zampieri N. 2011. Motor neuron position and topographic order imposed by β- and γ-catenin activities. Cell 147:641–52 [Google Scholar]
  47. Domanitskaya E, Wacker A, Mauti O, Baeriswyl T, Esteve P. et al. 2010. Sonic hedgehog guides post-crossing commissural axons both directly and indirectly by regulating Wnt activity. J. Neurosci. 30:11167–76 [Google Scholar]
  48. Dougherty KJ, Zagoraiou L, Satoh D, Rozani I, Doobar S. et al. 2013. Locomotor rhythm generation linked to the output of spinal Shox2 excitatory interneurons. Neuron 80:920–33 [Google Scholar]
  49. Duboule D. 1998. Vertebrate Hox gene regulation: clustering and/or colinearity?. Curr. Opin. Genet. Dev. 8:514–18 [Google Scholar]
  50. Dudanova I, Kao TJ, Herrmann JE, Zheng B, Kania A, Klein R. 2012. Genetic evidence for a contribution of EphA:ephrinA reverse signaling to motor axon guidance. J. Neurosci. 32:5209–15 [Google Scholar]
  51. Dudanova I, Klein R. 2013. Integration of guidance cues: parallel signaling and crosstalk. Trends Neurosci. 36:295–304 [Google Scholar]
  52. Dyck J, Lanuza GM, Gosgnach S. 2012. Functional characterization of dI6 interneurons in the neonatal mouse spinal cord. J. Neurophysiol. 107:3256–66 [Google Scholar]
  53. Eccles JC, Eccles RM, Lundberg A. 1957. The convergence of monosynaptic excitatory afferents on to many different species of α motoneurones. J. Physiol. 137:22–50 [Google Scholar]
  54. Esposito MS, Capelli P, Arber S. 2014. Brainstem nucleus MdV mediates skilled forelimb motor tasks. Nature 508:351–56 [Google Scholar]
  55. Farinas I, Jones KR, Backus C, Wang XY, Reichardt LF. 1994. Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 369:658–61 [Google Scholar]
  56. Fetcho JR. 1992. The spinal motor system in early vertebrates and some of its evolutionary changes. Brain Behav. Evol. 40:82–97 [Google Scholar]
  57. Fetcho JR, McLean DL. 2010. Some principles of organization of spinal neurons underlying locomotion in zebrafish and their implications. Ann. N. Y. Acad. Sci. 1198:94–104 [Google Scholar]
  58. Fink AJ, Croce KR, Huang ZJ, Abbott LF, Jessell TM, Azim E. 2014. Presynaptic inhibition of spinal sensory feedback ensures smooth movement. Nature 509:43–48 [Google Scholar]
  59. Francius C, Harris A, Rucchin V, Hendricks TJ, Stam FJ. et al. 2013. Identification of multiple subsets of ventral interneurons and differential distribution along the rostrocaudal axis of the developing spinal cord. PLOS ONE 8:e70325 [Google Scholar]
  60. Frank E. 1990. The formation of specific synaptic connections between muscle sensory and motor neurons in the absence of coordinated patterns of muscle activity. J. Neurosci. 10:2250–60 [Google Scholar]
  61. Fukuhara K, Imai F, Ladle DR, Katayama K, Leslie JR. et al. 2013. Specificity of monosynaptic sensory-motor connections imposed by repellent Sema3E-PlexinD1 signaling. Cell Rep. 5:748–58 [Google Scholar]
  62. Gallarda BW, Bonanomi D, Muller D, Brown A, Alaynick WA. et al. 2008. Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling. Science 320:233–36 [Google Scholar]
  63. Goetz C, Pivetta C, Arber S. 2015. Distinct limb and trunk premotor circuits establish laterality in the spinal cord. Neuron 85:131–44 [Google Scholar]
  64. Gore BB, Wong KG, Tessier-Lavigne M. 2008. Stem cell factor functions as an outgrowth-promoting factor to enable axon exit from the midline intermediate target. Neuron 57:501–10 [Google Scholar]
  65. Gosgnach S, Lanuza GM, Butt SJ, Saueressig H, Zhang Y. et al. 2006. V1 spinal neurons regulate the speed of vertebrate locomotor outputs. Nature 440:215–19 [Google Scholar]
  66. Goulding M. 2009. Circuits controlling vertebrate locomotion: moving in a new direction. Nat. Rev. Neurosci. 10:507–18 [Google Scholar]
  67. Grillner S. 2006. Biological pattern generation: the cellular and computational logic of networks in motion. Neuron 52:751–66 [Google Scholar]
  68. Grillner S, Manira AE. 2015. The intrinsic operation of the networks that make us locomote. Curr. Opin. Neurobiol. 31C:244–49 [Google Scholar]
  69. Guo T, Mandai K, Condie BG, Wickramasinghe SR, Capecchi MR, Ginty DD. 2011. An evolving NGF-Hoxd1 signaling pathway mediates development of divergent neural circuits in vertebrates. Nat. Neurosci. 14:31–36 [Google Scholar]
  70. Hantman AW, Jessell TM. 2010. Clarke's column neurons as the focus of a corticospinal corollary circuit. Nat. Neurosci. 13:1233–39 [Google Scholar]
  71. Helmbacher F, Schneider-Maunoury S, Topilko P, Tiret L, Charnay P. 2000. Targeting of the EphA4 tyrosine kinase receptor affects dorsal/ventral pathfinding of limb motor axons. Development 127:3313–24 [Google Scholar]
  72. Hoheisel U, Lehmann-Willenbrock E, Mense S. 1989. Termination patterns of identified group II and III afferent fibres from deep tissues in the spinal cord of the cat. Neuroscience 28:495–507 [Google Scholar]
  73. Honig MG, Frase PA, Camilli SJ. 1998. The spatial relationships among cutaneous, muscle sensory and motoneuron axons during development of the chick hindlimb. Development 125:995–1004 [Google Scholar]
  74. Huettl RE, Soellner H, Bianchi E, Novitch BG, Huber AB. 2011. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb. PLOS Biol. 9:e1001020 [Google Scholar]
  75. Isa T, Ohki Y, Alstermark B, Pettersson LG, Sasaki S. 2007. Direct and indirect cortico-motoneuronal pathways and control of hand/arm movements. Physiology 22:145–52 [Google Scholar]
  76. Islam SM, Shinmyo Y, Okafuji T, Su Y, Naser IB. et al. 2009. Draxin, a repulsive guidance protein for spinal cord and forebrain commissures. Science 323:388–93 [Google Scholar]
  77. Jankowska E. 2001. Spinal interneuronal systems: identification, multifunctional character and reconfigurations in mammals. J. Physiol. 533:31–40 [Google Scholar]
  78. Jankowska E, Edgley S. 1993. Interactions between pathways controlling posture and gait at the level of spinal interneurones in the cat. Prog. Brain Res. 97:161–71 [Google Scholar]
  79. Jessell TM. 2000. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1:20–29 [Google Scholar]
  80. Jung H, Dasen JS. 2015. Evolution of patterning systems and circuit elements for locomotion. Dev. Cell 32:408–22 [Google Scholar]
  81. Jung H, Lacombe J, Mazzoni EO, Liem KF Jr, Grinstein J. et al. 2010. Global control of motor neuron topography mediated by the repressive actions of a single Hox gene. Neuron 67:781–96 [Google Scholar]
  82. Jung H, Mazzoni EO, Soshnikova N, Hanley O, Venkatesh B. et al. 2014. Evolving Hox activity profiles govern diversity in locomotor systems. Dev. Cell 29:171–87 [Google Scholar]
  83. Kania A. 2014. Spinal motor neuron migration and the significance of topographic organization in the nervous system. Adv. Exp. Med. Biol. 800:133–48 [Google Scholar]
  84. Kania A, Jessell TM. 2003. Topographic motor projections in the limb imposed by LIM homeodomain protein regulation of ephrin-A:EphA interactions. Neuron 38:581–96 [Google Scholar]
  85. Kania A, Johnson RL, Jessell TM. 2000. Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb. Cell 102:161–73 [Google Scholar]
  86. Kao TJ, Kania A. 2011. Ephrin-mediated cis-attenuation of Eph receptor signaling is essential for spinal motor axon guidance. Neuron 71:76–91 [Google Scholar]
  87. Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS. et al. 1996. Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Cell 87:175–85 [Google Scholar]
  88. Kiehn O. 2011. Development and functional organization of spinal locomotor circuits. Curr. Opin. Neurobiol. 21:100–9 [Google Scholar]
  89. Kiehn O, Butt SJ. 2003. Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord. Prog. Neurobiol. 70:347–61 [Google Scholar]
  90. Kinoshita M, Matsui R, Kato S, Hasegawa T, Kasahara H. et al. 2012. Genetic dissection of the circuit for hand dexterity in primates. Nature 487:235–38 [Google Scholar]
  91. Klein R, Silos-Santiago I, Smeyne RJ, Lira SA, Brambilla R. et al. 1994. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature 368:249–51 [Google Scholar]
  92. Kramer ER, Knott L, Su F, Dessaud E, Krull CE. et al. 2006. Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway selection in the limb. Neuron 50:35–47 [Google Scholar]
  93. Krumlauf R. 1994. Hox genes in vertebrate development. Cell 78:191–201 [Google Scholar]
  94. Kullander K, Butt SJ, Lebret JM, Lundfald L, Restrepo CE. et al. 2003. Role of EphA4 and EphrinB3 in local neuronal circuits that control walking. Science 299:1889–92 [Google Scholar]
  95. Lacombe J, Hanley O, Jung H, Philippidou P, Surmeli G. et al. 2013. Genetic and functional modularity of Hox activities in the specification of limb-innervating motor neurons. PLOS Genet. 9:e1003184 [Google Scholar]
  96. Landmesser L. 1978. The development of motor projection patterns in the chick hind limb. J. Physiol. 284:391–414 [Google Scholar]
  97. Landmesser L, Honig MG. 1986. Altered sensory projections in the chick hind limb following the early removal of motoneurons. Dev. Biol. 118:511–31 [Google Scholar]
  98. Landmesser LT. 2001. The acquisition of motoneuron subtype identity and motor circuit formation. Int. J. Dev. Neurosci. 19:175–82 [Google Scholar]
  99. Lanuza GM, Gosgnach S, Pierani A, Jessell TM, Goulding M. 2004. Genetic identification of spinal interneurons that coordinate left-right locomotor activity necessary for walking movements. Neuron 42:375–86 [Google Scholar]
  100. Lawrence DG, Kuypers HG. 1968. The functional organization of the motor system in the monkey. I. The effects of bilateral pyramidal lesions. Brain 91:1–14 [Google Scholar]
  101. Lemon RN. 2008. Descending pathways in motor control. Annu. Rev. Neurosci. 31:195–218 [Google Scholar]
  102. Levine AJ, Hinckley CA, Hilde KL, Driscoll SP, Poon TH. et al. 2014. Identification of a cellular node for motor control pathways. Nat. Neurosci. 17:586–93 [Google Scholar]
  103. Li LY, Wang Z, Sedy J, Quazi R, Walro JM. et al. 2006. Neurotrophin-3 ameliorates sensory-motor deficits in Er81-deficient mice. Dev. Dyn. 235:3039–50 [Google Scholar]
  104. Liu JP, Laufer E, Jessell TM. 2001. Assigning the positional identity of spinal motor neurons: rostrocaudal patterning of Hox-c expression by FGFs, Gdf11, and retinoids. Neuron 32:997–1012 [Google Scholar]
  105. Luria V, Krawchuk D, Jessell TM, Laufer E, Kania A. 2008. Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb. Neuron 60:1039–53 [Google Scholar]
  106. Lyuksyutova AI, Lu CC, Milanesio N, King LA, Guo N. et al. 2003. Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302:1984–88 [Google Scholar]
  107. Matise MP, Lance-Jones C. 1996. A critical period for the specification of motor pools in the chick lumbosacral spinal cord. Development 122:659–69 [Google Scholar]
  108. McGinnis W, Krumlauf R. 1992. Homeobox genes and axial patterning. Cell 68:283–302 [Google Scholar]
  109. Mears SC, Frank E. 1997. Formation of specific monosynaptic connections between muscle spindle afferents and motoneurons in the mouse. J. Neurosci. 17:3128–35 [Google Scholar]
  110. Mendell LM, Henneman E. 1968. Terminals of single Ia fibers—distribution within a pool of 300 homonymous motor neurons. Science 160:96–98 [Google Scholar]
  111. Mendelson B, Frank E. 1991. Specific monosynaptic sensory-motor connections form in the absence of patterned neural activity and motoneuronal cell death. J. Neurosci. 11:1390–403 [Google Scholar]
  112. Miri A, Azim E, Jesse TM. 2013. Edging toward entelechy in motor control. Neuron 80:827–34 [Google Scholar]
  113. Muller D, Cherukuri P, Henningfeld K, Poh CH, Wittler L. et al. 2014. Dlk1 promotes a fast motor neuron biophysical signature required for peak force execution. Science 343:1264–66 [Google Scholar]
  114. Nawabi H, Briancon-Marjollet A, Clark C, Sanyas I, Takamatsu H. et al. 2010. A midline switch of receptor processing regulates commissural axon guidance in vertebrates. Genes Dev. 24:396–410 [Google Scholar]
  115. Palmesino E, Rousso DL, Kao TJ, Klar A, Laufer E. et al. 2010. Foxp1 and Lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling. PLOS Biol. 8:e1000446 [Google Scholar]
  116. Panayi H, Panayiotou E, Orford M, Genethliou N, Mean R. et al. 2010. Sox1 is required for the specification of a novel p2-derived interneuron subtype in the mouse ventral spinal cord. J. Neurosci. 30:12274–80 [Google Scholar]
  117. Parra LM, Zou Y. 2010. Sonic hedgehog induces response of commissural axons to Semaphorin repulsion during midline crossing. Nat. Neurosci. 13:29–35 [Google Scholar]
  118. Patel TD, Kramer I, Kucera J, Niederkofler V, Jessell TM. et al. 2003. Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents. Neuron 38:403–16 [Google Scholar]
  119. Paixão S, Balijepalli A, Serradj N, Niu J, Luo W. et al. 2013. EphrinB3/EphA4-mediated guidance of ascending and descending spinal tracts. Neuron 80:1407–20 [Google Scholar]
  120. Pecho-Vrieseling E, Sigrist M, Yoshida Y, Jessell TM, Arber S. 2009. Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition. Nature 459:842–46 [Google Scholar]
  121. Peng CY, Yajima H, Burns CE, Zon LI, Sisodia SS. et al. 2007. Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord. Neuron 53:813–27 [Google Scholar]
  122. Philippidou P, Dasen JS. 2013. Hox genes: choreographers in neural development, architects of circuit organization. Neuron 80:12–34 [Google Scholar]
  123. Philippidou P, Walsh CM, Aubin J, Jeannotte L, Dasen JS. 2012. Sustained Hox5 gene activity is required for respiratory motor neuron development. Nat. Neurosci. 15:1636–44 [Google Scholar]
  124. Pivetta C, Esposito MS, Sigrist M, Arber S. 2014. Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin. Cell 156:537–48 [Google Scholar]
  125. Poulet JF, Hedwig B. 2007. New insights into corollary discharges mediated by identified neural pathways. Trends Neurosci. 30:14–21 [Google Scholar]
  126. Price SR, De Marco Garcia NV, Ranscht B, Jessell TM. 2002. Regulation of motor neuron pool sorting by differential expression of type II cadherins. Cell 109:205–16 [Google Scholar]
  127. Rabe Bernhardt N, Memic F, Gezelius H, Thiebes AL, Vallstedt A, Kullander K. 2012. DCC mediated axon guidance of spinal interneurons is essential for normal locomotor central pattern generator function. Dev. Biol. 366:279–89 [Google Scholar]
  128. Rabe N, Gezelius H, Vallstedt A, Memic F, Kullander K. 2009. Netrin-1–dependent spinal interneuron subtypes are required for the formation of left-right alternating locomotor circuitry. J. Neurosci. 29:15642–49 [Google Scholar]
  129. Rousso DL, Gaber ZB, Wellik D, Morrisey EE, Novitch BG. 2008. Coordinated actions of the forkhead protein Foxp1 and Hox proteins in the columnar organization of spinal motor neurons. Neuron 59:226–40 [Google Scholar]
  130. Sabatier C, Plump AS, Le M, Brose K, Tamada A. et al. 2004. The divergent Robo family protein Rig-1/Robo3 is a negative regulator of Slit responsiveness required for midline crossing by commissural axons. Cell 117:157–69 [Google Scholar]
  131. Scott SA. 1988. Skin sensory innervation patterns in embryonic chick hindlimbs deprived of motoneurons. Dev. Biol. 126:362–74 [Google Scholar]
  132. Scott SA. 1992. Sensory Neurons: Diversity, Development, and Plasticity New York: Oxford Univ. Press
  133. Serafini T, Colamarino SA, Leonardo ED, Wang H, Beddington R. et al. 1996. Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell 87:1001–14 [Google Scholar]
  134. Serradj N, Paixão S, Sobocki T, Feinberg M, Klein R. et al. 2014. EphA4-mediated ipsilateral corticospinal tract misprojections are necessary for bilateral voluntary movements but not bilateral stereotypic locomotion. J. Neurosci. 34:5211–21 [Google Scholar]
  135. Shah V, Drill E, Lance-Jones C. 2004. Ectopic expression of Hoxd10 in thoracic spinal segments induces motoneurons with a lumbosacral molecular profile and axon projections to the limb. Dev. Dyn. 231:43–56 [Google Scholar]
  136. Sharma K, Leonard AE, Lettieri K, Pfaff SL. 2000. Genetic and epigenetic mechanisms contribute to motor neuron pathfinding. Nature 406:515–19 [Google Scholar]
  137. Sherrington CS. 1906. The Integrative Action of the Nervous System New York: Scribner
  138. Shirasaki R, Lewcock JW, Lettieri K, Pfaff SL. 2006. FGF as a target-derived chemoattractant for developing motor axons genetically programmed by the LIM code. Neuron 50:841–53 [Google Scholar]
  139. Shirasaki R, Pfaff SL. 2002. Transcriptional codes and the control of neuronal identity. Annu. Rev. Neurosci. 25:251–81 [Google Scholar]
  140. Snider WD. 1994. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77:627–38 [Google Scholar]
  141. Sockanathan S, Jessell TM. 1998. Motor neuron–derived retinoid signaling specifies the subtype identity of spinal motor neurons. Cell 94:503–14 [Google Scholar]
  142. Soundararajan P, Fawcett JP, Rafuse VF. 2010. Guidance of postural motoneurons requires MAPK/ERK signaling downstream of fibroblast growth factor receptor 1. J. Neurosci. 30:6595–606 [Google Scholar]
  143. Stein E, Tessier-Lavigne M. 2001. Hierarchical organization of guidance receptors: silencing of netrin attraction by Slit through a Robo/DCC receptor complex. Science 291:1928–38 [Google Scholar]
  144. Stepien AE, Tripodi M, Arber S. 2010. Monosynaptic rabies virus reveals premotor network organization and synaptic specificity of cholinergic partition cells. Neuron 68:456–72 [Google Scholar]
  145. Surmeli G, Akay T, Ippolito GC, Tucker PW, Jessell TM. 2011. Patterns of spinal sensory-motor connectivity prescribed by a dorsoventral positional template. Cell 147:653–65 [Google Scholar]
  146. Swanson GJ, Lewis J. 1986. Sensory nerve routes in chick wing buds deprived of motor innervation. J. Embryol. Exp. Morphol. 95:37–52 [Google Scholar]
  147. Talpalar AE, Bouvier J, Borgius L, Fortin G, Pierani A, Kiehn O. 2013. Dual-mode operation of neuronal networks involved in left-right alternation. Nature 500:85–88 [Google Scholar]
  148. Talpalar AE, Endo T, Low P, Borgius L, Hagglund M. et al. 2011. Identification of minimal neuronal networks involved in flexor-extensor alternation in the mammalian spinal cord. Neuron 71:1071–84 [Google Scholar]
  149. Thor S, Andersson SG, Tomlinson A, Thomas JB. 1999. A LIM-homeodomain combinatorial code for motor-neuron pathway selection. Nature 397:76–80 [Google Scholar]
  150. Todorov E. 2004. Optimality principles in sensorimotor control. Nat. Neurosci. 7:907–15 [Google Scholar]
  151. Tosney KW, Hageman MS. 1989. Different subsets of axonal guidance cues are essential for sensory neurite outgrowth to cutaneous and muscle targets in the dorsal ramus of the embryonic chick. J. Exp. Zool. 251:232–44 [Google Scholar]
  152. Tosney KW, Landmesser LT. 1985. Growth cone morphology and trajectory in the lumbosacral region of the chick embryo. J. Neurosci. 5:2345–58 [Google Scholar]
  153. Tripodi M, Stepien AE, Arber S. 2011. Motor antagonism exposed by spatial segregation and timing of neurogenesis. Nature 479:61–66 [Google Scholar]
  154. Tsuchida T, Ensini M, Morton SB, Baldassare M, Edlund T. et al. 1994. Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes. Cell 79:957–70 [Google Scholar]
  155. Vrieseling E, Arber S. 2006. Target-induced transcriptional control of dendritic patterning and connectivity in motor neurons by the ETS gene Pea3. Cell 127:1439–52 [Google Scholar]
  156. Wall NR, Wickersham IR, Cetin A, De La Parra M, Callaway EM. 2010. Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus. PNAS 107:21848–53 [Google Scholar]
  157. Wang L, Klein R, Zheng B, Marquardt T. 2011. Anatomical coupling of sensory and motor nerve trajectory via axon tracking. Neuron 71:263–77 [Google Scholar]
  158. Wang G, Scott SA. 1999. Independent development of sensory and motor innervation patterns in embryonic chick hindlimbs. Dev. Biol. 208:324–36 [Google Scholar]
  159. Wilson JM, Hartley R, Maxwell DJ, Todd AJ, Lieberam I. et al. 2005. Conditional rhythmicity of ventral spinal interneurons defined by expression of the Hb9 homeodomain protein. J. Neurosci. 25:5710–19 [Google Scholar]
  160. Windhorst U. 2007. Muscle proprioceptive feedback and spinal networks. Brain Res. Bull. 73:155–202 [Google Scholar]
  161. Wolpert DM, Miall RC. 1996. Forward models for physiological motor control. Neural Netw. 9:1265–79 [Google Scholar]
  162. Wu Y, Wang G, Scott SA, Capecchi MR. 2008. Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons. Development 135:171–82 [Google Scholar]
  163. Yam PT, Kent CB, Morin S, Farmer WT, Alchini R. et al. 2012. 14-3-3 proteins regulate a cell-intrinsic switch from Sonic Hedgehog–mediated commissural axon attraction to repulsion after midline crossing. Neuron 76:735–49 [Google Scholar]
  164. Yuasa-Kawada J, Kinoshita-Kawada M, Wu G, Rao Y, Wu JY. 2009. Midline crossing and Slit responsiveness of commissural axons require USP33. Nat. Neurosci. 12:1087–89 [Google Scholar]
  165. Zagoraiou L, Akay T, Martin JF, Brownstone RM, Jessell TM, Miles GB. 2009. A cluster of cholinergic premotor interneurons modulates mouse locomotor activity. Neuron 64:645–62 [Google Scholar]
  166. Zarin AA, Asadzadeh J, Hokamp K, McCartney D, Yang L. et al. 2014. A transcription factor network coordinates attraction, repulsion, and adhesion combinatorially to control motor axon pathway selection. Neuron 81:1297–311 [Google Scholar]
  167. Zhang J, Lanuza GM, Britz O, Wang Z, Siembab VC. et al. 2014. V1 and v2b interneurons secure the alternating flexor-extensor motor activity mice require for limbed locomotion. Neuron 82:138–50 [Google Scholar]
  168. Zhang Y, Narayan S, Geiman E, Lanuza GM, Velasquez T. et al. 2008. V3 spinal neurons establish a robust and balanced locomotor rhythm during walking. Neuron 60:84–96 [Google Scholar]
  169. Zhong G, Sharma K, Harris-Warrick RM. 2011. Frequency-dependent recruitment of V2a interneurons during fictive locomotion in the mouse spinal cord. Nat. Commun. 2:274 [Google Scholar]
  170. Zou Y, Stoeckli E, Chen H, Tessier-Lavigne M. 2000. Squeezing axons out of the gray matter: a role for Slit and Semaphorin proteins from midline and ventral spinal cord. Cell 102:363–75 [Google Scholar]
/content/journals/10.1146/annurev-cellbio-100814-125155
Loading
/content/journals/10.1146/annurev-cellbio-100814-125155
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error