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Smooth-muscle-specific expression of neurotrophin-3 in mouse embryonic and neonatal gastrointestinal tract

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Abstract

Vagal gastrointestinal (GI) afferents are essential for the regulation of eating, body weight, and digestion. However, their functional organization and the way that this develops are poorly understood. Neurotrophin-3 (NT-3) is crucial for the survival of vagal sensory neurons and is expressed in the developing GI tract, possibly contributing to their survival and to other aspects of vagal afferent development. The identification of the functions of this peripheral NT-3 thus requires a detailed understanding of the localization and timing of its expression in the developing GI tract. We have studied embryos and neonates expressing the lacZ reporter gene from the NT-3 locus and found that NT-3 is expressed predominantly in the smooth muscle of the outer GI wall of the stomach, intestines, and associated blood vessels and in the stomach lamina propria and esophageal epithelium. NT-3 expression has been detected in the mesenchyme of the GI wall by embryonic day 12.5 (E12.5) and becomes restricted to smooth muscle and lamina propria by E15.5, whereas its expression in blood vessels and esophageal epithelium is first observed at E15.5. Expression in most tissues is maintained at least until postnatal day 4. The lack of colocalization of β-galactosidase and markers for myenteric ganglion cell types suggests that NT-3 is not expressed in these ganglia. Therefore, NT-3 expression in the GI tract is largely restricted to smooth muscle at ages when vagal axons grow into the GI tract, and when vagal mechanoreceptors form in smooth muscle, consistent with its role in these processes and in vagal sensory neuron survival.

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References

  • Airaksinen MS, Koltzenburg M, Lewin GR, Masu Y, Helbig C, Wolf E, Brem G, Toyka KV, Thoenen H, Meyer M (1996) Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation. Neuron 16:287–295

    PubMed  Google Scholar 

  • Albers KM, Perrone TN, Goodness TP, Jones ME, Green MA, Davis BM (1996) Cutaneous overexpression of NT-3 increases sensory and sympathetic neuron number and enhances touch dome and hair follicle innervation. J Cell Biol 134:487–497

    PubMed  Google Scholar 

  • Arvanov VL, Seebach BS, Mendell LM (2000) NT-3 evokes an LTP-like facilitation of AMPA/kainate receptor-mediated synaptic transmission in the neonatal rat spinal cord. J Neurophysiol 84:752–758

    PubMed  Google Scholar 

  • Barami K, Iversen K, Furneaux H, Goldman SA (1995) Hu protein as an early marker of neuronal phenotypic differentiation by subependymal zone cells of the adult songbird forebrain. J Neurobiol 28:82–101

    PubMed  Google Scholar 

  • Bennett JL, Zeiler SR, Jones KR (1999) Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye. Invest Ophthalmol Vis Sci 40:2996–3005

    PubMed  Google Scholar 

  • Bernd P (2008) The role of neurotrophins during early development. Gene Expr 14:241–250

    PubMed  Google Scholar 

  • Botchkarev VA, Botchkareva NV, Peters EM, Paus R (2004) Epithelial growth control by neurotrophins: leads and lessons from the hair follicle. Prog Brain Res 146:493–513

    PubMed  Google Scholar 

  • Brady R, Zaidi SI, Mayer C, Katz DM (1999) BDNF is a target-derived survival factor for arterial baroreceptor and chemoafferent primary sensory neurons. J Neurosci 19:2131–2142

    PubMed  Google Scholar 

  • Buchman VL, Davies AM (1993) Different neurotrophins are expressed and act in a developmental sequence to promote the survival of embryonic sensory neurons. Development 118:989–1001

    PubMed  Google Scholar 

  • Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM (1996) Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 93:12008–12013

    PubMed  Google Scholar 

  • Campagnolo L, Russo MA, Puglianiello A, Favale A, Siracusa G (2001) Mesenchymal cell precursors of peritubular smooth muscle cells of the mouse testis can be identified by the presence of the p75 neurotrophin receptor. Biol Reprod 64:464–472

    PubMed  Google Scholar 

  • Chalazonitis A (1996) Neurotrophin-3 as an essential signal for the developing nervous system. Mol Neurobiol 12:39–53

    PubMed  Google Scholar 

  • Chalazonitis A, Pham TD, Rothman TP, DiStefano PS, Bothwell M, Blair-Flynn J, Tessarollo L, Gershon MD (2001) Neurotrophin-3 is required for the survival-differentiation of subsets of developing enteric neurons. J Neurosci 21:5620–5636

    PubMed  Google Scholar 

  • Coates PJ, Lorimore SA, Rigat BA, Lane DP, Wright EG (2001) Induction of endogenous beta-galactosidase by ionizing radiation complicates the analysis of p53-LacZ transgenic mice. Oncogene 20:7096–7097

    PubMed  Google Scholar 

  • De Giorgio R, Arakawa J, Wetmore CJ, Sternini C (2000) Neurotrophin-3 and neurotrophin receptor immunoreactivity in peptidergic enteric neurons. Peptides 21:1421–1426

    PubMed  Google Scholar 

  • Donovan MJ, Miranda RC, Kraemer R, McCaffrey TA, Tessarollo L, Mahadeo D, Sharif S, Kaplan DR, Tsoulfas P, Parada L, et al (1995) Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury. Am J Pathol 147:309–324

    PubMed  Google Scholar 

  • Durbec PL, Larsson-Blomberg LB, Schuchardt A, Costantini F, Pachnis V (1996) Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts. Development 122:349–358

    PubMed  Google Scholar 

  • ElShamy WM, Ernfors P (1997) Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 complement and cooperate with each other sequentially during visceral neuron development. J Neurosci 17:8667–8675

    PubMed  Google Scholar 

  • El-Yazbi AF, Schulz R, Daniel EE (2007) Differential inhibitory control of circular and longitudinal smooth muscle layers of Balb/C mouse small intestine. Auton Neurosci 131:36–44

    PubMed  Google Scholar 

  • Ernfors P (2001) Local and target-derived actions of neurotrophins during peripheral nervous system development. Cell Mol Life Sci 58:1036–1044

    PubMed  Google Scholar 

  • Ernfors P, Wetmore C, Eriksdotter-Nilsson M, Bygdeman M, Stromberg I, Olson L, Persson H (1991) The nerve growth factor receptor gene is expressed in both neuronal and non-neuronal tissues in the human fetus. Int J Dev Neurosci 9:57–66

    PubMed  Google Scholar 

  • Ernfors P, Merlio JP, Persson H (1992) Cells expressing messenger-RNA for neurotrophins and their receptors during embryonic rat development. Eur J NeuroSci 4:1140–1158

    PubMed  Google Scholar 

  • Ernfors P, Lee KF, Kucera J, Jaenisch R (1994) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77:503–512

    PubMed  Google Scholar 

  • Farinas I (1999) Neurotrophin actions during the development of the peripheral nervous system. Microsc Res Tech 45:233–242

    PubMed  Google Scholar 

  • Farinas I, Jones KR, Backus C, Wang XY, Reichardt LF (1994) Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 369:658–661

    PubMed  Google Scholar 

  • Farinas I, Yoshida CK, Backus C, Reichardt LF (1996) Lack of neurotrophin-3 results in death of spinal sensory neurons and premature differentiation of their precursors. Neuron 17:1065–1078

    PubMed  Google Scholar 

  • Farinas I, Wilkinson GA, Backus C, Reichardt LF, Patapoutian A (1998) Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo. Neuron 21:325–334

    PubMed  Google Scholar 

  • Farinas I, Jones KR, Tessarollo L, Vigers AJ, Huang E, Kirstein M, Caprona DC de, Coppola V, Backus C, Reichardt LF, Fritzsch B (2001) Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression. J Neurosci 21:6170–6180

    PubMed  Google Scholar 

  • Fox EA (2000) The previously identified r3/r5 repressor may require the cooperation of additional negative elements for rhombomere restriction of Hoxb1. Brain Res Dev Brain Res 120:151–164

    PubMed  Google Scholar 

  • Fox EA (2006) A genetic approach for investigating vagal sensory roles in regulation of gastrointestinal function and food intake. Auton Neurosci 126–127:9–29

    PubMed  Google Scholar 

  • Fox EA, Phillips RJ, Martinson FA, Baronowsky EA, Powley TL (2000) Vagal afferent innervation of smooth muscle in the stomach and duodenum of the mouse: morphology and topography. J Comp Neurol 428:558–576

    PubMed  Google Scholar 

  • Fox EA, Phillips RJ, Baronowsky EA, Byerly MS, Jones S, Powley TL (2001) Neurotrophin-4 deficient mice have a loss of vagal intraganglionic mechanoreceptors from the small intestine and a disruption of short-term satiety. J Neurosci 21:8602–8615

    PubMed  Google Scholar 

  • Fox EA, Phillips RJ, Byerly MS, Baronowsky EA, Chi MM, Powley TL (2002) Selective loss of vagal intramuscular mechanoreceptors in mice mutant for steel factor, the c-Kit receptor ligand. Anat Embryol 205:325–342

    PubMed  Google Scholar 

  • Francis N, Farinas I, Brennan C, Rivas-Plata K, Backus C, Reichardt L, Landis S (1999) NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors. Dev Biol 210:411–427

    PubMed  Google Scholar 

  • Genc B, Ozdinler PH, Mendoza AE, Erzurumlu RS (2004) A chemoattractant role for NT-3 in proprioceptive axon guidance. PLoS Biol 2:e403

    PubMed  Google Scholar 

  • Grimes ML, Zhou J, Beattie EC, Yuen EC, Hall DE, Valletta JS, Topp KS, LaVail JH, Bunnett NW, Mobley WC (1996) Endocytosis of activated TrkA: evidence that nerve growth factor induces formation of signaling endosomes. J Neurosci 16:7950–7964

    PubMed  Google Scholar 

  • Grimes ML, Beattie E, Mobley WC (1997) A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA. Proc Natl Acad Sci USA 94:9909–9914

    PubMed  Google Scholar 

  • Helke CJ, Adryan KM, Fedorowicz J, Zhuo H, Park JS, Curtis R, Radley HE, Distefano PS (1998) Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat. J Comp Neurol 393:102–117

    PubMed  Google Scholar 

  • Heller RS, Stoffers DA, Hussain MA, Miller CP, Habener JF (1998) Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum. Gastroenterology 115:381–387

    PubMed  Google Scholar 

  • Hess DM, Scott MO, Potluri S, Pitts EV, Cisterni C, Balice-Gordon RJ (2007) Localization of TrkC to Schwann cells and effects of neurotrophin-3 signaling at neuromuscular synapses. J Comp Neurol 501:465–482

    PubMed  Google Scholar 

  • Ho A, Lievore A, Patierno S, Kohlmeier SE, Tonini M, Sternini C (2003) Neurochemically distinct classes of myenteric neurons express the mu-opioid receptor in the guinea pig ileum. J Comp Neurol 458:404–411

    PubMed  Google Scholar 

  • Hoff S, Zeller F, Weyhern CW von, Wegner M, Schemann M, Michel K, Ruhl A (2008) Quantitative assessment of glial cells in the human and guinea pig enteric nervous system with an anti-Sox8/9/10 antibody. J Comp Neurol 509:356–371

    PubMed  Google Scholar 

  • Holmberg A, Hagg U, Fritsche R, Holmgren S (2001) Occurrence of neurotrophin receptors and transmitters in the developing Xenopus gut. Cell Tissue Res 306:35–47

    PubMed  Google Scholar 

  • Huang EJ, Wilkinson GA, Farinas I, Backus C, Zang K, Wong SL, Reichardt LF (1999) Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC. Development 126:2191–2203

    PubMed  Google Scholar 

  • Huber LJ, Chao MV (1995) Mesenchymal and neuronal cell expression of the p75 neurotrophin receptor gene occur by different mechanisms. Dev Biol 167:227–238

    PubMed  Google Scholar 

  • Huber K, Kuehnel F, Wyatt S, Davies AM (2000) TrkB expression and early sensory neuron survival are independent of endogenous BDNF. J Neurosci Res 59:372–378

    PubMed  Google Scholar 

  • Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373:347–349

    PubMed  Google Scholar 

  • Jahn T, Seipel P, Coutinho S, Urschel S, Schwarz K, Miething C, Serve H, Peschel C, Duyster J (2002) Analysing c-kit internalization using a functional c-kit-EGFP chimera containing the fluorochrome within the extracellular domain. Oncogene 21:4508–4520

    PubMed  Google Scholar 

  • Jones KR, Farinas I, Backus C, Reichardt LF (1994) Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 76:989–999

    PubMed  Google Scholar 

  • Kablar B, Tajbakhsh S, Rudnicki MA (2000) Transdifferentiation of esophageal smooth to skeletal muscle is myogenic bHLH factor-dependent. Development 127:1627–1639

    PubMed  Google Scholar 

  • Kawazoe Y, Sekimoto T, Araki M, Takagi K, Araki K, Yamamura K (2002) Region-specific gastrointestinal Hox code during murine embryonal gut development. Dev Growth Differ 44:77–84

    PubMed  Google Scholar 

  • Kluppel M, Huizinga JD, Malysz J, Bernstein A (1998) Developmental origin and Kit-dependent development of the interstitial cells of Cajal in the mammalian small intestine. Dev Dyn 211:60–71

    PubMed  Google Scholar 

  • Kuruvilla R, Zweifel LS, Glebova NO, Lonze BE, Valdez G, Ye H, Ginty DD (2004) A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell 118:243–255

    PubMed  Google Scholar 

  • Lamballe F, Klein R, Barbacid M (1991) trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell 66:967–979

    PubMed  Google Scholar 

  • Lamballe F, Smeyne RJ, Barbacid M (1994) Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system. J Neurosci 14:14–28

    PubMed  Google Scholar 

  • Le Douarin NM, Kalcheim C (1999) The neural crest, 2nd edn. Cambridge University Press, Cambridge

    Google Scholar 

  • Lentz SI, Knudson CM, Korsmeyer SJ, Snider WD (1999) Neurotrophins support the development of diverse sensory axon morphologies. J Neurosci 19:1038–1048

    PubMed  Google Scholar 

  • Lewis EB (1978) A gene complex controlling segmentation in Drosophila. Nature 276:565–570

    PubMed  Google Scholar 

  • Li S, Qiu F, Xu A, Price SM, Xiang M (2004) Barhl1 regulates migration and survival of cerebellar granule cells by controlling expression of the neurotrophin-3 gene. J Neurosci 24:3104–3114

    PubMed  Google Scholar 

  • Liebl DJ, Tessarollo L, Palko ME, Parada LF (1997) Absence of sensory neurons before target innervation in brain-derived neurotrophic factor-, neurotrophin 3-, and TrkC-deficient embryonic mice. J Neurosci 17:9113–9121

    PubMed  Google Scholar 

  • Lin Z, Gao N, Hu HZ, Liu S, Gao C, Kim G, Ren J, Xia Y, Peck OC, Wood JD (2002) Immunoreactivity of Hu proteins facilitates identification of myenteric neurones in guinea-pig small intestine. Neurogastroenterol Motil 14:197–204

    PubMed  Google Scholar 

  • Lin A, Lourenssen S, Stanzel RD, Blennerhassett MG (2005) Nerve growth factor sensitivity is broadly distributed among myenteric neurons of the rat colon. J Comp Neurol 490:194–206

    PubMed  Google Scholar 

  • Lojda Z, Havrankova E, Slaby J (1974) Histochemical demonstration of the intestinal hetero-beta-galactosidase (glucosidase). Histochemistry 42:271–286

    PubMed  Google Scholar 

  • Lommatzsch M, Quarcoo D, Schulte-Herbruggen O, Weber H, Virchow JC, Renz H, Braun A (2005) Neurotrophins in murine viscera: a dynamic pattern from birth to adulthood. Int J Dev Neurosci 23:495–500

    PubMed  Google Scholar 

  • MacInnis BL, Campenot RB (2002) Retrograde support of neuronal survival without retrograde transport of nerve growth factor. Science 295:1536–1539

    PubMed  Google Scholar 

  • Martinez-Ceballos E, Chambon P, Gudas LJ (2005) Differences in gene expression between wild type and Hoxa1 knockout embryonic stem cells after retinoic acid treatment or leukemia inhibitory factor (LIF) removal. J Biol Chem 280:16484–16498

    PubMed  Google Scholar 

  • Marusich MF, Furneaux HM, Henion PD, Weston JA (1994) Hu neuronal proteins are expressed in proliferating neurogenic cells. J Neurobiol 25:143–155

    PubMed  Google Scholar 

  • McGinnis W, Krumlauf R (1992) Homeobox genes and axial patterning. Cell 68:283–302

    PubMed  Google Scholar 

  • Ming G, Lohof AM, Zheng JQ (1997) Acute morphogenic and chemotropic effects of neurotrophins on cultured embryonic Xenopus spinal neurons. J Neurosci 17:7860–7871

    PubMed  Google Scholar 

  • Murphy MC, Fox EA (2007) Anterograde tracing method using DiI to label vagal innervation of the embryonic and early postnatal mouse gastrointestinal tract. J Neurosci Methods 163:213–225

    PubMed  Google Scholar 

  • Murphy EM, Defontgalland D, Costa M, Brookes SJ, Wattchow DA (2007) Quantification of subclasses of human colonic myenteric neurons by immunoreactivity to Hu, choline acetyltransferase and nitric oxide synthase. Neurogastroenterol Motil 19:126–134

    PubMed  Google Scholar 

  • Niwa H, Hayakawa K, Yamamoto M, Itoh T, Mitsuma T, Sobue G (2002) Differential age-dependent trophic responses of nodose, sensory, and sympathetic neurons to neurotrophins and GDNF: potencies for neurite extension in explant culture. Neurochem Res 27:485–496

    PubMed  Google Scholar 

  • Nobuhisa I, Takizawa M, Takaki S, Inoue H, Okita K, Ueno M, Takatsu K, Taga T (2003) Regulation of hematopoietic development in the aorta-gonad-mesonephros region mediated by Lnk adaptor protein. Mol Cell Biol 23:8486–8494

    PubMed  Google Scholar 

  • Oestreicher E, Knipper M, Arnold A, Zenner HP, Felix D (2000) Neurotrophin 3 potentiates glutamatergic responses of IHC afferents in the cochlea in vivo. Eur J Neurosci 12:1584–1590

    PubMed  Google Scholar 

  • Patapoutian A, Wold BJ, Wagner RA (1995) Evidence for developmentally programmed transdifferentiation in mouse esophageal muscle. Science 270:1818–1821

    PubMed  Google Scholar 

  • Patapoutian A, Backus C, Kispert A, Reichardt LF (1999) Regulation of neurotrophin-3 expression by epithelial-mesenchymal interactions: the role of Wnt factors. Science 283:1180–1183

    PubMed  Google Scholar 

  • Paves H, Saarma M (1997) Neurotrophins as in vitro growth cone guidance molecules for embryonic sensory neurons. Cell Tissue Res 290:285–297

    PubMed  Google Scholar 

  • Peng C, Fan S, Li X, Fan X, Ming M, Sun Z, Le W (2007) Overexpression of pitx3 upregulates expression of BDNF and GDNF in SH-SY5Y cells and primary ventral mesencephalic cultures. FEBS Lett 581:1357–1361

    PubMed  Google Scholar 

  • Pham TA, Impey S, Storm DR, Stryker MP (1999) CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period. Neuron 22:63–72

    PubMed  Google Scholar 

  • Pham T, Guerrini S, Wong H, Reeve J Jr, Sternini C (2002) Distribution of galanin receptor 1 immunoreactivity in the rat stomach and small intestine. J Comp Neurol 450:292–302

    PubMed  Google Scholar 

  • Pitera JE, Smith VV, Thorogood P, Milla PJ (1999) Coordinated expression of 3' hox genes during murine embryonal gut development: an enteric Hox code. Gastroenterology 117:1339–1351

    PubMed  Google Scholar 

  • Pollock RA, Jay G, Bieberich CJ (1992) Altering the boundaries of Hox3.1 expression: evidence for antipodal gene regulation. Cell 71:911–923

    PubMed  Google Scholar 

  • Raab M, Worl J, Brehmer A, Neuhuber WL (2003) Reduction of NT-3 or TrkC results in fewer putative vagal mechanoreceptors in the mouse esophagus. Auton Neurosci 108:22–31

    PubMed  Google Scholar 

  • Ratcliffe EM, Setru SU, Chen JJ, Li ZS, D'Autreaux F, Gershon MD (2006) Netrin/DCC-mediated attraction of vagal sensory axons to the fetal mouse gut. J Comp Neurol 498:567–580

    PubMed  Google Scholar 

  • Ratcliffe EM, D'Autreaux F, Gershon MD (2008) Laminin terminates the Netrin/DCC mediated attraction of vagal sensory axons. Dev Neurobiol 68:960–971

    PubMed  Google Scholar 

  • Rishniw M, Xin HB, Deng KY, Kotlikoff MI (2003) Skeletal myogenesis in the mouse esophagus does not occur through transdifferentiation. Genesis 36:81–82

    PubMed  Google Scholar 

  • Sanchez-Ramos J, Song S, Dailey M, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Zigova T, Sanberg PR, Snyder EY (2000) The X-gal caution in neural transplantation studies. Cell Transplant 9:657–667

    PubMed  Google Scholar 

  • Sang Q, Young HM (1998) The origin and development of the vagal and spinal innervation of the external muscle of the mouse esophagus. Brain Res 809:253–268

    PubMed  Google Scholar 

  • Sauer B (1998) Inducible gene targeting in mice using the Cre/lox system. Methods 14:381–392

    PubMed  Google Scholar 

  • Scarisbrick IA, Jones EG, Isackson PJ (1993) Coexpression of mRNAs for NGF, BDNF, and NT-3 in the cardiovascular system of the pre- and postnatal rat. J Neurosci 13:875–893

    PubMed  Google Scholar 

  • Schrans-Stassen BH, Kant HJ van de, Rooij DG de, Pelt AM van (1999) Differential expression of c-kit in mouse undifferentiated and differentiating type A spermatogonia. Endocrinology 140:5894–5900

    PubMed  Google Scholar 

  • Sekimoto T, Yoshinobu K, Yoshida M, Kuratani S, Fujimoto S, Araki M, Tajima N, Araki K, Yamamura K (1998) Region-specific expression of murine Hox genes implies the Hox code-mediated patterning of the digestive tract. Genes Cells 3:51–64

    PubMed  Google Scholar 

  • Shuba MF, Melenevs'ka NV, Filippov IB, Miroshnychenko MS (2006) Molecular mechanisms of receptor-dependent signaling in the cells of the longitudinal and circular intestinal smooth muscles. Ukr Biokhim Zh 78:15–21

    PubMed  Google Scholar 

  • Snider WD (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77:627–638

    PubMed  Google Scholar 

  • Spencer NJ, Dickson EJ, Hennig GW, Smith TK (2006) Sensory elements within the circular muscle are essential for mechanotransduction of ongoing peristaltic reflex activity in guinea-pig distal colon. J Physiol (Lond) 576:519–531

    Google Scholar 

  • Sternini C, Su D, Arakawa J, Giorgio R de, Rickman DW, Davis BM, Albers KM, Brecha NC (1996) Cellular localization of Pan-trk immunoreactivity and trkC mRNA in the enteric nervous system. J Comp Neurol 368:597–607

    PubMed  Google Scholar 

  • Sundqvist M, Holmgren S (2004) Neurotrophin receptors and enteric neuronal development during metamorphosis in the amphibian Xenopus laevis. Cell Tissue Res 316:45–54

    PubMed  Google Scholar 

  • Takahashi Y, Imanaka T, Takano T (1998) Spatial pattern of smooth muscle differentiation is specified by the epithelium in the stomach of mouse embryo. Dev Dyn 212:448–460

    PubMed  Google Scholar 

  • Tessarollo L, Tsoulfas P, Donovan MJ, Palko ME, Blair-Flynn J, Hempstead BL, Parada LF (1997) Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis. Proc Natl Acad Sci USA 94:14776–14781

    PubMed  Google Scholar 

  • Tojo H, Takami K, Kaisho Y, Nakata M, Abe T, Shiho O, Igarashi K (1995) Neurotrophin-3 is expressed in the posterior lobe of mouse cerebellum, but does not affect the cerebellar development. Neurosci Lett 192:169–172

    PubMed  Google Scholar 

  • Torihashi S, Ward SM, Sanders KM (1997) Development of c-Kit-positive cells and the onset of electrical rhythmicity in murine small intestine. Gastroenterology 112:144–155

    PubMed  Google Scholar 

  • Tucker KL, Meyer M, Barde YA (2001) Neurotrophins are required for nerve growth during development. Nat Neurosci 4:29–37

    PubMed  Google Scholar 

  • Ulupinar E, Jacquin MF, Erzurumlu RS (2000) Differential effects of NGF and NT-3 on embryonic trigeminal axon growth patterns. J Comp Neurol 425:202–218

    PubMed  Google Scholar 

  • Vannucchi MG, Faussone-Pellegrini MS (2000) Synapse formation during neuron differentiation: an in situ study of the myenteric plexus during murine embryonic life. J Comp Neurol 425:369–381

    PubMed  Google Scholar 

  • Vigers AJ, Baquet ZC, Jones KR (2000) Expression of neurotrophin-3 in the mouse forebrain: insights from a targeted LacZ reporter. J Comp Neurol 416:398–415

    PubMed  Google Scholar 

  • Vigers AJ, Bottger B, Baquet ZC, Finger TE, Jones KR (2003) Neurotrophin-3 is expressed in a discrete subset of olfactory receptor neurons in the mouse. J Comp Neurol 463:221–235

    PubMed  Google Scholar 

  • Ward SM, Burns AJ, Torihashi S, Sanders KM (1994) Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol (Lond) 480:91–97

    Google Scholar 

  • Weiss DJ, Liggitt D, Clark JG (1999) Histochemical discrimination of endogenous mammalian beta-galactosidase activity from that resulting from lac-Z gene expression. Histochem J 31:231–236

    PubMed  Google Scholar 

  • Wilkinson GA, Farinas I, Backus C, Yoshida CK, Reichardt LF (1996) Neurotrophin-3 is a survival factor in vivo for early mouse trigeminal neurons. J Neurosci 16:7661–7669

    PubMed  Google Scholar 

  • Xiang Z, Burnstock G (2004) Development of nerves expressing P2X3 receptors in the myenteric plexus of rat stomach. Histochem Cell Biol 122:111–119

    PubMed  Google Scholar 

  • Yahagi N, Kosaki R, Ito T, Mitsuhashi T, Shimada H, Tomita M, Takahashi T, Kosaki K (2004) Position-specific expression of Hox genes along the gastrointestinal tract. Congenit Anom Kyoto 44:18–26

    PubMed  Google Scholar 

  • Yan H, Keast JR (2008) Neurturin regulates postnatal differentiation of parasympathetic pelvic ganglion neurons, initial axonal projections, and maintenance of terminal fields in male urogenital organs. J Comp Neurol 507:1169–1183

    PubMed  Google Scholar 

  • Yee CL, Jones KR, Finger TE (2003) Brain-derived neurotrophic factor is present in adult mouse taste cells with synapses. J Comp Neurol 459:15–24

    PubMed  Google Scholar 

  • Young HM, Turner KN, Bergner AJ (2005) The location and phenotype of proliferating neural-crest-derived cells in the developing mouse gut. Cell Tissue Res 320:1–9

    PubMed  Google Scholar 

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Acknowledgements

We are grateful to Louis Reichardt (University of California, San Francisco) for NT-3 lacZ mice, to Thomas Finger (University of Colorado, Denver) for the guinea pig β-galactosidase antibody, and to Tom Karam for animal care and breeding. Preliminary reports of the present findings were presented in abstract form at the IVth International Congress of the International Society for Autonomic Neuroscience, in a review based on this presentation (Fox 2006), and in abstract form at the 36th and 38th annual meetings of the Society for Neuroscience.

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  1. Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue University, 703 Third Street, West Lafayette, IN, 47907, USA

    Edward A. Fox & Jennifer McAdams

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  1. Edward A. Fox
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  2. Jennifer McAdams
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Correspondence to Edward A. Fox.

Additional information

This work was supported by NIH grant NS046716.

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Supplementary Fig. 1

NT-3 expression patterns in the large intestine at E13.5. Photomicrographs of X-gal-stained large intestine sections are shown on the left (a,c,e) and adjacent (b and f) or semi-adjacent (d) sections counterstained with neutral red to their right. NT-3 expression in the large intestine within the abdomen of some embryos at E13.5 (a-f) occurred throughout the mesenchyme (a,b), but in other specimens at some anterior-posterior levels (c-f) the outer muscle wall had begun to differentiate, and in parallel NT-3 expression became largely restricted to this tissue layer. There was no expression in the epithelium. Scale bars = 50 μm; the bar in d also applies to a-c and the bar in f also applies to e. Abbreviations as for Figs. 1-3 (GIF 575 KB)

High resolution image file (TIF 14.9 MB)

Supplementary Fig. 2

NT-3 expression patterns in the large intestine at E15.5. Photomicrographs of X-gal-stained large intestine sections (a,c) are shown to the left of semi-adjacent sections counterstained with neutral red (b,d). NT-3 expression in the large intestine at E15.5 (a-d) occurred in the circular smooth muscle layer (a-d), and was equally strong in (c), weaker in (d), or absent from (a,b) different segments of the longitudinal smooth muscle layer. By E15.5 folding of the mucosa had begun. Scale bar in d = 100 (m and it applies to a-c. Mesentery, mst; other abbreviations as for Figs. 2 and 3 Supplementary Fig. 3 NT-3 expression pattern in the large intestine at P4. Photomicrographs of X-gal-stained large intestine sections (a,c) are shown to the left of semi-adjacent sections counterstained with neutral red (b,d). At P4, the predominant NT-3 expression in the large intestine occurred in the circular smooth muscle layer (a-d). At this age the mucosa appeared mature. Scale bar in b = 200 (m and in d = 50 (m and they also apply to a and c, respectively. Abbreviations as for Fig. 2 (GIF 348 KB)

High resolution image file (TIF 10.2 MB)

Supplementary Fig. 3

NT-3 expression pattern in the large intestine at P4 (abbreviations as for Fig. 2 in main text). Photomicrographs of X-gal-stained large intestine sections (a, c) are shown left and semi-adjacent sections counterstained with neutral red right (b, d). At P4, the predominant NT-3 expression in the large intestine occurred in the circular smooth muscle layer. At this age, the mucosa appeared mature. Bars 200 μm (b), 50 μm (d). (GIF 340 KB)

High resolution image file (TIF 8.46 MB)

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Fox, E.A., McAdams, J. Smooth-muscle-specific expression of neurotrophin-3 in mouse embryonic and neonatal gastrointestinal tract. Cell Tissue Res 340, 267–286 (2010). https://doi.org/10.1007/s00441-010-0959-7

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