Journal of Molecular Neuroscience

, Volume 54, Issue 2, pp 199–210 | Cite as

Protocadherin 11 X Regulates Differentiation and Proliferation of Neural Stem Cell In Vitro and In Vivo

  • Peng Zhang
  • Cuiying Wu
  • Ning Liu
  • Lijun Niu
  • Zhongjie Yan
  • Yanyan Feng
  • Ruxiang Xu
Article

Abstract

Protocadherin 11 X-linked (Pcdh11x) protein is a member of the cadherin superfamily with established roles in cell adhesion. Previous studies have shown the molecular biology and possible relevance of Pcdh11x with neurological disease in humans. However, little is known about the neurophysiological function of Pcdh11x in neural development. Here, we verified that Pcdh11x is primarily expressed in various brain areas including the cortex, hippocampus, and ventricular/subventricular zone (VZ/SVZ) at different embryonic stages. Furthermore, both in vitro and in vivo experiments showed that Pcdh11x decreased neural differentiation but increased the neural proliferation. These observations demonstrate a crucial function for Pcdh11x during the development of central nervous system.

Keywords

Protocadherin 11 X-linked protein Neural stem cell Differentiation Proliferation Migration 

Notes

Acknowledgments

This study was funded by Military Medical Project (BWS11J002, BWS12J010) and National Natural Science Foundation (no. 30973096). Thanks to Zhang Xiao Chong at Ju Lu Hospital for her help with the experiment. We thank Elsevier Language Editing (Project no.: 39443) for assisting in the preparation of this manuscript. The authors would like to thank all the anonymous reviewers for their valuable comments on how to improve the quality of this paper.

Conflict of Interest

No conflicts of interest, financial or otherwise, are declared by the authors.

References

  1. Ahn K, Huh JW, Kim DS, Ha HS, Kim YJ, Lee JR, Kim HS (2010) Quantitative analysis of alternative transcripts of human PCDH11X/Y genes. Am J Med Genet B Neuropsychiatr Genet 153B:736–744PubMedGoogle Scholar
  2. Barnabe-Heider F, Wasylnka JA, Fernandes KJ, Porsche C, Sendtner M, Kaplan DR, Miller FD (2005) Evidence that embryonic neurons regulate the onset of cortical gliogenesis via cardiotrophin-1. Neuron 48:253–265PubMedCrossRefGoogle Scholar
  3. Benson DL, Colman DR, Huntley GW (2001) Molecules, maps and synapse specificity. Nat Rev Neurosci 2:899–909PubMedCrossRefGoogle Scholar
  4. Blanco P, Sargent CA, Boucher CA, Mitchell M, Affara NA (2000) Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain. Mamm Genome 11:906–914PubMedCrossRefGoogle Scholar
  5. Blanco-Arias P, Sargent CA, Affara NA (2004) Protocadherin X ( PCDHX) and Y ( PCDHY) genes; multiple mRNA isoforms encoding variant signal peptides and cytoplasmic domains. Mamm Genome 15:41–52PubMedCrossRefGoogle Scholar
  6. Bozdagi O, Shan W, Tanaka H, Benson DL, Huntley GW (2000) Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation. Neuron 28:245–259PubMedCrossRefGoogle Scholar
  7. Bruses JL (2000) Cadherin-mediated adhesion at the interneuronal synapse. Curr Opin Cell Biol 12:593–597PubMedCrossRefGoogle Scholar
  8. Farioli-Vecchioli S, Saraulli D, Costanzi M, Pacioni S, Cina I, Aceti M, Micheli L, Bacci A, Cestari V, Tirone F (2008) The timing of differentiation of adult hippocampal neurons is crucial for spatial memory. PLoS Biol 6:e246PubMedCentralPubMedCrossRefGoogle Scholar
  9. Frank M, Kemler R (2002) Protocadherins. Curr Opin Cell Biol 14:557–562PubMedCrossRefGoogle Scholar
  10. Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778PubMedCrossRefGoogle Scholar
  11. Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E (1999) Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci U S A 96:5263–5267PubMedCentralPubMedCrossRefGoogle Scholar
  12. Haubensak W, Attardo A, Denk W, Huttner WB (2004) Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A 101:3196–3201PubMedCentralPubMedCrossRefGoogle Scholar
  13. Hertel N, Krishna K, Nuernberger M, Redies C (2008) A cadherin-based code for the divisions of the mouse basal ganglia. J Comp Neurol 508:511–528PubMedCrossRefGoogle Scholar
  14. Hirabayashi Y, Itoh Y, Tabata H, Nakajima K, Akiyama T, Masuyama N, Gotoh Y (2004) The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development 131:2791–2801PubMedCrossRefGoogle Scholar
  15. Hirano S, Yan Q, Suzuki ST (1999) Expression of a novel protocadherin, OL-protocadherin, in a subset of functional systems of the developing mouse brain. J Neurosci 19:995–1005PubMedGoogle Scholar
  16. Jessberger S, Romer B, Babu H, Kempermann G (2005) Seizures induce proliferation and dispersion of doublecortin-positive hippocampal progenitor cells. Exp Neurol 196:342–351PubMedCrossRefGoogle Scholar
  17. Kim SY, Yasuda S, Tanaka H, Yamagata K, Kim H (2011) Non-clustered protocadherin. Cell Adhes Migr 5:97–105CrossRefGoogle Scholar
  18. Kowalczyk T, Pontious A, Englund C, Daza RA, Bedogni F, Hodge R, Attardo A, Bell C, Huttner WB, Hevner RF (2009) Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. Cereb Cortex 19:2439–2450PubMedCentralPubMedCrossRefGoogle Scholar
  19. Leber SM, Breedlove SM, Sanes JR (1990) Lineage, arrangement, and death of clonally related motoneurons in chick spinal cord. J Neurosci 10:2451–2462PubMedGoogle Scholar
  20. Lopes AM, Ross N, Close J, Dagnall A, Amorim A, Crow TJ (2006) Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in brain. Hum Genet 119:267–275PubMedCrossRefGoogle Scholar
  21. Luckner R, Obst-Pernberg K, Hirano S, Suzuki ST, Redies C (2001) Granule cell raphes in the developing mouse cerebellum. Cell Tissue Res 303:159–172PubMedCrossRefGoogle Scholar
  22. Morishita H, Yagi T (2007) Protocadherin family: diversity, structure, and function. Curr Opin Cell Biol 19:584–592PubMedCrossRefGoogle Scholar
  23. Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409:714–720PubMedCrossRefGoogle Scholar
  24. Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7:136–144PubMedCrossRefGoogle Scholar
  25. Persengiev SP, Zhu X, Green MR (2004) Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 10:12–18PubMedCentralPubMedCrossRefGoogle Scholar
  26. Priddle TH, Crow TJ (2013) Protocadherin 11X/Y a human-specific gene pair: an immunohistochemical survey of fetal and adult brains. Cereb Cortex 23:1933–1941PubMedCentralPubMedCrossRefGoogle Scholar
  27. Rash BG, Lim HD, Breunig JJ, Vaccarino FM (2011) FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. J Neurosci 31:15604–15617PubMedCentralPubMedCrossRefGoogle Scholar
  28. Redies C (2000) Cadherins in the central nervous system. Prog Neurobiol 61:611–648PubMedCrossRefGoogle Scholar
  29. Redies C, Vanhalst K, Roy F (2005) delta-Protocadherins: unique structures and functions. Cell Mol Life Sci 62:2840–2852PubMedCrossRefGoogle Scholar
  30. Saito T (2006) In vivo electroporation in the embryonic mouse central nervous system. Nat Protoc 1:1552–1558PubMedCrossRefGoogle Scholar
  31. Semizarov D, Frost L, Sarthy A, Kroeger P, Halbert DN, Fesik SW (2003) Specificity of short interfering RNA determined through gene expression signatures. Proc Natl Acad Sci U S A 100:6347–6352PubMedCentralPubMedCrossRefGoogle Scholar
  32. Shapiro L, Colman DR (1999) The diversity of cadherins and implications for a synaptic adhesive code in the CNS. Neuron 23:427–430PubMedCrossRefGoogle Scholar
  33. Speevak MD, Farrell SA (2011) Non-syndromic language delay in a child with disruption in the Protocadherin11X/Y gene pair. Am J Med Genet B Neuropsychiatr Genet 156B:484–489PubMedCrossRefGoogle Scholar
  34. Suzuki ST (1996) Protocadherins and diversity of the cadherin superfamily. J Cell Sci 109(Pt 11):2609–2611PubMedGoogle Scholar
  35. Tanaka H, Shan W, Phillips GR, Arndt K, Bozdagi O, Shapiro L, Huntley GW, Benson DL, Colman DR (2000) Molecular modification of N-cadherin in response to synaptic activity. Neuron 25:93–107PubMedCrossRefGoogle Scholar
  36. Vanhalst K, Kools P, Staes K, van Roy F, Redies C (2005) delta-Protocadherins: a gene family expressed differentially in the mouse brain. Cell Mol Life Sci 62:1247–1259PubMedCrossRefGoogle Scholar
  37. Walsh C, Reid C (1995) Cell lineage and patterns of migration in the developing cortex. CIBA Found Symp 193:21–40, discussion 59–70PubMedGoogle Scholar
  38. Weickert CS, Elashoff M, Richards AB, Sinclair D, Bahn S, Paabo S, Khaitovich P, Webster MJ (2009) Transcriptome analysis of male-female differences in prefrontal cortical development. Mol Psychiatry 14:558–561PubMedCrossRefGoogle Scholar
  39. Woodhead GJ, Mutch CA, Olson EC, Chenn A (2006) Cell-autonomous beta-catenin signaling regulates cortical precursor proliferation. J Neurosci 26:12620–12630PubMedCentralPubMedCrossRefGoogle Scholar
  40. Wu Q, Maniatis T (1999) A striking organization of a large family of human neural cadherin-like cell adhesion genes. Cell 97:779–790PubMedCrossRefGoogle Scholar
  41. Yagi T, Takeichi M (2000) Cadherin superfamily genes: functions, genomic organization, and neurologic diversity. Genes Dev 14:1169–1180PubMedGoogle Scholar
  42. Yamagata K, Andreasson KI, Sugiura H, Maru E, Dominique M, Irie Y, Miki N, Hayashi Y, Yoshioka M, Kaneko K, Kato H, Worley PF (1999) Arcadlin is a neural activity-regulated cadherin involved in long term potentiation. J Biol Chem 274:19473–1979PubMedCrossRefGoogle Scholar
  43. Yoshida K, Sugano S (1999) Identification of a novel protocadherin gene (PCDH11) on the human XY homology region in Xq21.3. Genomics 62:540–543PubMedCrossRefGoogle Scholar
  44. Zhang J, Woodhead GJ, Swaminathan SK, Noles SR, McQuinn ER, Pisarek AJ, Stocker AM, Mutch CA, Funatsu N, Chenn A (2010) Cortical neural precursors inhibit their own differentiation via N-cadherin maintenance of beta-catenin signaling. Dev Cell 18:472–479PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Peng Zhang
    • 1
    • 2
  • Cuiying Wu
    • 2
  • Ning Liu
    • 2
  • Lijun Niu
    • 2
  • Zhongjie Yan
    • 2
    • 3
  • Yanyan Feng
    • 2
  • Ruxiang Xu
    • 1
    • 2
  1. 1.Bayi Brain Hospital, Bayi Clinical Medical InstituteSouthern Medical UniversityBeijingChina
  2. 2.Bayi Brain Hospital, The Military General Hospital of Beijing PLABeijingChina
  3. 3.Department of Neurosurgerythe Second Hospital of Hebei Medical UniversityShijiazhuangChina

Personalised recommendations