Abstract
How are precise connectivity to peripheral targets and corresponding sensory-motor networks established during developmental innervation of the vertebrate extremities? The formation of functional sensory-motor circuits requires highly appropriate temporal and spatial regulation of axon growth which is achieved through the combination of different molecular mechanisms such as communication between heterotypic fiber systems, axon-environment, or axon-glia interactions that ensure proper fasciculation and accurate pathfinding to distal targets. Family members of the class 3 semaphorins and their cognate receptors, the neuropilins, were shown to govern various events during wiring of central and peripheral circuits, with mice lacking Sema3-Npn signaling showing deficits in timing of growth, selective fasciculation, guidance fidelity, and coupling of sensory axon growth to motor axons at developmental time points. Given the accuracy with which these processes have to interact in a stepwise manner, deficiency of the smallest cog in the wheel may impact severely on the faithful establishment and functionality of peripheral circuitries, ultimately leading to behavioral impairments or even cause the death of the animal. Reliable quantitative analyses of sensory-motor fasciculation, extension, and guidance of axons to their cognate target muscles and the skin during development, but also assessment of physiological and behavioral consequences at adult age, are therefore a necessity to extend our understanding of the molecular mechanisms of peripheral circuit formation. In this chapter we provide a detailed methodology to characterize class 3 semaphorin-mediated effects on peripheral sensory and motor axon pathfinding and connectivity during embryonic development.
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References
Pradat PF, Dib M (2009) Biomarkers in amyotrophic lateral sclerosis: facts and future horizons. Mol Diagn Ther 13(2):115–125
Kostova FV, Williams VC, Heemskerk J et al (2007) Spinal muscular atrophy: classification, diagnosis, management, pathogenesis, and future research directions. J Child Neurol 22(8):926–945
Mueller BK, Yamashita T, Schaffar G et al (2006) The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system. Philos Trans R Soc Lond B Biol Sci 361(1473):1513–1529
Maier IC, Schwab ME (2006) Sprouting, regeneration and circuit formation in the injured spinal cord: factors and activity. Philos Trans R Soc Lond B Biol Sci 361(1473):1611–1634
Huber AB, Kolodkin AL, Ginty DD et al (2003) Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26:509–563
Raper JA, Bastiani MJ, Goodman CS (1983) Guidance of neuronal growth cones: selective fasciculation in the grasshopper embryo. Cold Spring Harb Symp Quant Biol 48(Pt 2):587–598
Cirulli V, Yebra M (2007) Netrins: beyond the brain. Nat Rev Mol Cell Biol 8(4):296–306
Castellani V (2013) Building spinal and brain commissures: axon guidance at the midline. ISRN Cell Biol 2013:21
Kidd T, Bland KS, Goodman CS (1999) Slit is the midline repellent for the robo receptor in Drosophila. Cell 96(6):785–794
Fritzsch B, Northcutt RG (1993) Cranial and spinal nerve organization in amphioxus and lampreys: evidence for an ancestral craniate pattern. Acta Anat (Basel) 148(2–3):96–109
Bonanomi D, Pfaff SL (2010) Motor axon pathfinding. Cold Spring Harb Perspect Biol 2(3):a001735
Kolodkin AL, Levengood DV, Rowe EG et al (1997) Neuropilin is a semaphorin III receptor. Cell 90(4):753–762
He Z, Tessier-Lavigne M (1997) Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90(4):739–751
Yazdani U, Terman JR (2006) The semaphorins. Genome Biol 7(3):211
Nawabi H, Briancon-Marjollet A, Clark C et al (2010) A midline switch of receptor processing regulates commissural axon guidance in vertebrates. Genes Dev 24(4):396–410
Zou Y, Stoeckli E, Chen H et al (2000) Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord. Cell 102(3):363–375
Mears SC, Frank E (1997) Formation of specific monosynaptic connections between muscle spindle afferents and motoneurons in the mouse. J Neurosci 17(9):3128–3135
Pecho-Vrieseling E, Sigrist M, Yoshida Y et al (2009) Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition. Nature 459(7248):842–846
Huber AB, Kania A, Tran TS et al (2005) Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron 48(6):949–964
Huettl RE, Huber AB (2011) Cranial nerve fasciculation and Schwann cell migration are impaired after loss of Npn-1., Dev Biol
Huettl RE, Soellner H, Bianchi E et al (2011) Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb. PLoS Biol 9(2), e1001020
Schwarz Q, Vieira JM, Howard B et al (2008) Neuropilin 1 and 2 control cranial gangliogenesis and axon guidance through neural crest cells. Development 135(9):1605–1613
Chen H, Bagri A, Zupicich JA et al (2000) Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections. Neuron 25(1):43–56
Finzsch M, Schreiner S, Kichko T et al (2010) Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage. J Cell Biol 189(4):701–712
Narayanan CH, Malloy RB (1974) Deafferentation studies on motor activity in the chick. I. Activity pattern of hindlimbs. J Exp Zool 189(2):163–176
Landmesser L, Honig MG (1986) Altered sensory projections in the chick hind limb following the early removal of motoneurons. Dev Biol 118(2):511–531
Wang G, Scott SA (1999) Independent development of sensory and motor innervation patterns in embryonic chick hindlimbs. Dev Biol 208(2):324–336
Wang L, Klein R, Zheng B et al (2011) Anatomical coupling of sensory and motor nerve trajectory via axon tracking. Neuron 71(2):263–277
Guthrie S (2007) Patterning and axon guidance of cranial motor neurons. Nat Rev Neurosci 8(11):859–871
Brockschnieder D, Pechmann Y, Sonnenberg-Riethmacher E et al (2006) An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus. Genesis 44(7):322–327
Dessaud E, Yang LL, Hill K et al (2007) Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism. Nature 450(7170):717–720
Wichterle H, Lieberam I, Porter JA et al (2002) Directed differentiation of embryonic stem cells into motor neurons. Cell 110(3):385–397
Pietri T, Eder O, Blanche M et al (2003) The human tissue plasminogen activator-Cre mouse: a new tool for targeting specifically neural crest cells and their derivatives in vivo. Dev Biol 259(1):176–187
Sullivan G (1962) Anatomy and embryology of the Wing Musculature of the domestic fowl (gallus). Aust J Zool 10(3):458–518
Hollyday M, Jacobson RD (1990) Location of motor pools innervating chick wing. J Comp Neurol 302(3):575–588
Gu C, Rodriguez ER, Reimert DV et al (2003) Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell 5(1):45–57
Kania A, Jessell TM (2003) Topographic motor projections in the limb imposed by LIM homeodomain protein regulation of ephrin-A:EphA interactions. Neuron 38(4):581–596
Luria V, Krawchuk D, Jessell TM et al (2008) Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb. Neuron 60(6):1039–1053
Surmeli G, Akay T, Ippolito GC et al (2011) Patterns of spinal sensory-motor connectivity prescribed by a dorsoventral positional template. Cell 147(3):653–665
Lindsay RM (1996) Role of neurotrophins and trk receptors in the development and maintenance of sensory neurons: an overview. Philos Trans R Soc Lond B Biol Sci 351(1338):365–373
Gallo G, Lefcort FB, Letourneau PC (1997) The trkA receptor mediates growth cone turning toward a localized source of nerve growth factor. J Neurosci 17(14):5445–5454
Delaurier A, Burton N, Bennett M et al (2008) The Mouse Limb Anatomy Atlas: an interactive 3D tool for studying embryonic limb patterning. BMC Dev Biol 8:83
Ugolini G (1995) Specificity of rabies virus as a transneuronal tracer of motor networks: transfer from hypoglossal motoneurons to connected second-order and higher order central nervous system cell groups. J Comp Neurol 356(3):457–480
Trojanowski JQ, Schmidt ML (1984) Interneuronal transfer of axonally transported proteins: studies with HRP and HRP conjugates of wheat germ agglutinin, cholera toxin and the B subunit of cholera toxin. Brain Res 311(2):366–369
Audouard E, Schakman O, Rene F et al (2012) The Onecut transcription factor HNF-6 regulates in motor neurons the formation of the neuromuscular junctions. PLoS One 7(12), e50509
Zhou Y, Gunput RA, Pasterkamp RJ (2008) Semaphorin signaling: progress made and promises ahead. Trends Biochem Sci 33(4):161–170
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Huettl, R.E., Huber, A.B. (2017). Characterizing Semaphorin-Mediated Effects on Sensory and Motor Axon Pathfinding and Connectivity During Embryonic Development. In: Terman, J. (eds) Semaphorin Signaling. Methods in Molecular Biology, vol 1493. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6448-2_32
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DOI: https://doi.org/10.1007/978-1-4939-6448-2_32
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