Advertisement

Acta Neuropathologica

, Volume 121, Issue 6, pp 721–735 | Cite as

New ependymal cells are born postnatally in two discrete regions of the mouse brain and support ventricular enlargement in hydrocephalus

  • Luis Federico Bátiz
  • Antonio J. Jiménez
  • Montserrat Guerra
  • Luis Manuel Rodríguez-Pérez
  • César D. Toledo
  • Karin Vio
  • Patricia Páez
  • José Manuel Pérez-Fígares
  • Esteban M. Rodríguez
Original Paper

Abstract

A heterogeneous population of ependymal cells lines the brain ventricles. The evidence about the origin and birth dates of these cell populations is scarce. Furthermore, the possibility that mature ependymal cells are born (ependymogenesis) or self-renewed (ependymal proliferation) postnatally is controversial. The present study was designed to investigate both phenomena in wild-type (wt) and hydrocephalic α-SNAP mutant (hyh) mice at different postnatal stages. In wt mice, proliferating cells in the ventricular zone (VZ) were only found in two distinct regions: the dorsal walls of the third ventricle and Sylvian aqueduct (SA). Most proliferating cells were monociliated and nestin+, likely corresponding to radial glial cells. Postnatal cumulative BrdU-labeling showed that most daughter cells remained in the VZ of both regions and they lost nestin-immunoreactivity. Furthermore, some labeled cells became multiciliated and GLUT-1+, indicating they were ependymal cells born postnatally. Postnatal pulse BrdU-labeling and Ki-67 immunostaining further demonstrated the presence of cycling multiciliated ependymal cells. In hydrocephalic mutants, the dorsal walls of the third ventricle and SA expanded enormously and showed neither ependymal disruption nor ventriculostomies. This phenomenon was sustained by an increased ependymogenesis. Consequently, in addition to the physical and geometrical mechanisms traditionally explaining ventricular enlargement in fetal-onset hydrocephalus, we propose that postnatal ependymogenesis could also play a role. Furthermore, as generation of new ependymal cells during postnatal stages was observed in distinct regions of the ventricular walls, such as the roof of the third ventricle, it may be a key mechanism involved in the development of human type 1 interhemispheric cysts.

Keywords

Radial glia Ependyma Proliferation Postnatal ependymogenesis Hydrocephalus Type 1 interhemispheric cyst 

Notes

Acknowledgments

We thank Mr. Genaro Alvial for his valuable technical support. This work was supported by Grants from Fondecyt-Chile 1070241 to EMR and 11090373 to LFB; PCI2006-A/-0669 and PS09/00376, Instituto de Salud Carlos III and Servicio Andaluz de Salud, Spain to AJJ.

Supplementary material

401_2011_799_MOESM1_ESM.doc (36 kb)
Supplementary material 1 (DOC 35 kb)

References

  1. 1.
    Aikawa H, Suzuki K (1986) Ultrastructural evidence of mitotic ependymal cells in 6-aminonicotinamide-treated suckling mice. Acta Neuropathol 70:71–74PubMedCrossRefGoogle Scholar
  2. 2.
    Banizs B, Pike MM, Millican CL et al (2005) Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development 132:5329–5339PubMedCrossRefGoogle Scholar
  3. 3.
    Barkovich AJ, Simon EM, Walsh CA (2001) Callosal agenesis with cyst: a better understanding and new classification. Neurology 56:220–227PubMedGoogle Scholar
  4. 4.
    Bátiz LF, Páez P, Jiménez AJ et al (2006) Heterogeneous expression of hydrocephalic phenotype in the hyh mice carrying a point mutation in alpha-SNAP. Neurobiol Dis 23:152–168PubMedCrossRefGoogle Scholar
  5. 5.
    Bátiz LF, Roales-Bujan R, Rodríguez-Pérez LM et al (2009) A simple PCR-based genotyping method for M105I mutation of alpha-SNAP enhances the study of early pathological changes in hyh phenotype. Mol Cell Probes 23:281–290PubMedCrossRefGoogle Scholar
  6. 6.
    Bronson RT, Lane PW (1990) Hydrocephalus with hop gait (hyh): a new mutation on chromosome 7 in the mouse. Brain Res Dev Brain Res 54:131–136PubMedCrossRefGoogle Scholar
  7. 7.
    Bruni JE (1998) Ependymal development, proliferation, and functions: a review. Microsc Res Tech 41:2–13PubMedCrossRefGoogle Scholar
  8. 8.
    Bruni JE, Clattenburg RE, Paterson JA (1983) Ependymal cells of the rat fourth ventricle: response to injury. Scan Electron Microsc 2:649–661Google Scholar
  9. 9.
    Bruni JE, Del Bigio MR, Clattenburg RE (1985) Ependyma: normal and pathological. A review of the literature. Brain Res 356:1–19PubMedGoogle Scholar
  10. 10.
    Bunn RC, King WD, Winkler MK, Fowlkes JL (2005) Early developmental changes in IGF-I, IGF-II, IGF binding protein-1, and IGF binding protein-3 concentration in the cerebrospinal fluid of children. Pediatr Res 58:89–93PubMedCrossRefGoogle Scholar
  11. 11.
    Chae TH, Kim S, Marz KE, Hanson PI, Walsh CA (2004) The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate. Nat Genet 36:264–270PubMedCrossRefGoogle Scholar
  12. 12.
    Dattatreyamurty B, Roux E, Horbinski C et al (2001) Cerebrospinal fluid contains biologically active bone morphogenetic protein-7. Exp Neurol 172:273–281PubMedCrossRefGoogle Scholar
  13. 13.
    Del Bigio MR (1995) The ependyma: a protective barrier between brain and cerebrospinal fluid. Glia 14:1–13PubMedCrossRefGoogle Scholar
  14. 14.
    Del Bigio MR (2001) Pathophysiologic consequences of hydrocephalus. Neurosurg Clin N Am 12:639–649 viiPubMedGoogle Scholar
  15. 15.
    Del Bigio MR (2010) Ependymal cells: biology and pathology. Acta Neuropathol 119:55–73PubMedCrossRefGoogle Scholar
  16. 16.
    Del Bigio MR, Bruni JE (1986) Reaction of rabbit lateral periventricular tissue to shunt tubing implants. J Neurosurg 64:932–940PubMedCrossRefGoogle Scholar
  17. 17.
    Del Bigio MR, Bruni JE (1988) Periventricular pathology in hydrocephalic rabbits before and after shunting. Acta Neuropathol 77:186–195PubMedGoogle Scholar
  18. 18.
    Domínguez-Pinos MD, Páez P, Jiménez AJ et al (2005) Ependymal denudation and alterations of the subventricular zone occur in human fetuses with a moderate communicating hydrocephalus. J Neuropathol Exp Neurol 64:595–604PubMedGoogle Scholar
  19. 19.
    Ferland RJ, Batiz LF, Neal J et al (2009) Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia. Hum Mol Genet 18:497–516PubMedCrossRefGoogle Scholar
  20. 20.
    Gotz M, Huttner WB (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6:777–788PubMedCrossRefGoogle Scholar
  21. 21.
    Hakim S, Venegas JG, Burton JD (1976) The physics of the cranial cavity, hydrocephalus and normal pressure hydrocephalus: mechanical interpretation and mathematical model. Surg Neurol 5:187–210PubMedGoogle Scholar
  22. 22.
    Hall PA, Levison DA, Woods AL et al (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162:285–294PubMedCrossRefGoogle Scholar
  23. 23.
    Hochhaus F, Koehne P, Schaper C et al (2001) Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus. BMC Pediatr 1:2PubMedCrossRefGoogle Scholar
  24. 24.
    Hong HK, Chakravarti A, Takahashi JS (2004) The gene for soluble N-ethylmaleimide sensitive factor attachment protein alpha is mutated in hydrocephaly with hop gait (hyh) mice. Proc Natl Acad Sci USA 101:1748–1753PubMedCrossRefGoogle Scholar
  25. 25.
    Ibanez-Tallon I, Pagenstecher A, Fliegauf M et al (2004) Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum Mol Genet 13:2133–2141PubMedCrossRefGoogle Scholar
  26. 26.
    Ino H, Chiba T (2000) Expression of proliferating cell nuclear antigen (PCNA) in the adult and developing mouse nervous system. Brain Res Mol Brain Res 78:163–174PubMedCrossRefGoogle Scholar
  27. 27.
    Jiménez AJ, García-Verdugo JM, González CA et al (2009) Disruption of the neurogenic niche in the subventricular zone of postnatal hydrocephalic hyh mice. J Neuropathol Exp Neurol 68:1006–1020PubMedCrossRefGoogle Scholar
  28. 28.
    Jiménez AJ, Tomé M, Páez P et al (2001) A programmed ependymal denudation precedes congenital hydrocephalus in the hyh mutant mouse. J Neuropathol Exp Neurol 60:1105–1119PubMedGoogle Scholar
  29. 29.
    Luo J, Shook BA, Daniels SB, Conover JC (2008) Subventricular zone-mediated ependyma repair in the adult mammalian brain. J Neurosci 28:3804–3813PubMedCrossRefGoogle Scholar
  30. 30.
    Mashayekhi F, Draper CE, Bannister CM, Pourghasem M, Owen-Lynch PJ, Miyan JA (2002) Deficient cortical development in the hydrocephalic Texas (H-Tx) rat: a role for CSF. Brain 125:1859–1874PubMedCrossRefGoogle Scholar
  31. 31.
    Mashayekhi F, Salehi Z (2005) Expression of nerve growth factor in cerebrospinal fluid of congenital hydrocephalic and normal children. Eur J Neurol 12:632–637PubMedCrossRefGoogle Scholar
  32. 32.
    Merkle FT, Alvarez-Buylla A (2006) Neural stem cells in mammalian development. Curr Opin Cell Biol 18:704–709PubMedCrossRefGoogle Scholar
  33. 33.
    Nagashima T, Tamaki N, Matsumoto S, Horwitz B, Seguchi Y (1987) Biomechanics of hydrocephalus: a new theoretical model. Neurosurgery 21:898–904PubMedCrossRefGoogle Scholar
  34. 34.
    Owen-Lynch PJ, Draper CE, Mashayekhi F, Bannister CM, Miyan JA (2003) Defective cell cycle control underlies abnormal cortical development in the hydrocephalic Texas rat. Brain 126:623–631PubMedCrossRefGoogle Scholar
  35. 35.
    Páez P, Bátiz LF, Roales-Bujan R et al (2007) Patterned neuropathologic events occurring in hyh congenital hydrocephalic mutant mice. J Neuropathol Exp Neurol 66:1082–1092PubMedCrossRefGoogle Scholar
  36. 36.
    Page RB (1975) Scanning electron microscopy of the ventricular system in normal and hydrocephalic rabbits. Preliminary report and atlas. J Neurosurg 42:646–664PubMedCrossRefGoogle Scholar
  37. 37.
    Page RB, Rosenstein JM, Dovey BJ, Leure-duPree AE (1979) Ependymal changes in experimental hydrocephalus. Anat Rec 194:83–103PubMedCrossRefGoogle Scholar
  38. 38.
    Pena A, Bolton MD, Whitehouse H, Pickard JD (1999) Effects of brain ventricular shape on periventricular biomechanics: a finite-element analysis. Neurosurgery 45:107–116 (discussion 116–118)PubMedCrossRefGoogle Scholar
  39. 39.
    Pérez-Fígares JM, Jiménez AJ, Pérez-Martin M et al (1998) Spontaneous congenital hydrocephalus in the mutant mouse hyh. Changes in the ventricular system and the subcommissural organ. J Neuropathol Exp Neurol 57:188–202PubMedCrossRefGoogle Scholar
  40. 40.
    Rodríguez EM (1976) The cerebrospinal fluid as a pathway in neuroendocrine integration. J Endocrinol 71:407–443PubMedCrossRefGoogle Scholar
  41. 41.
    Rodríguez EM, Blázquez JL, Guerra M (2010) The design of barriers in the hypothalamus allows the median eminence and the arcuate nucleus to enjoy private milieus: the former opens to the portal blood and the latter to the cerebrospinal fluid. Peptides 31:757–776PubMedCrossRefGoogle Scholar
  42. 42.
    Sarnat HB (1992) Regional differentiation of the human fetal ependyma: immunocytochemical markers. J Neuropathol Exp Neurol 51:58–75PubMedCrossRefGoogle Scholar
  43. 43.
    Sarnat HB (1992) Role of human fetal ependyma. Pediatr Neurol 8:163–178PubMedCrossRefGoogle Scholar
  44. 44.
    Sarnat HB (1995) Ependymal reactions to injury. A review. J Neuropathol Exp Neurol 54:1–15PubMedCrossRefGoogle Scholar
  45. 45.
    Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322PubMedCrossRefGoogle Scholar
  46. 46.
    Silva-Alvarez C, Carrasco M, Balmaceda-Aguilera C et al (2005) Ependymal cell differentiation and GLUT1 expression is a synchronous process in the ventricular wall. Neurochem Res 30:1227–1236PubMedCrossRefGoogle Scholar
  47. 47.
    Sival DA, Guerra M, Den Dunnen WFA et al (2011) Neuroependymal denudation is in progress in full-term human foetal spina bifida aperta. Brain Pathol. doi:  10.1111/j.1750-3639.2010.00432.x
  48. 48.
    Spassky N, Merkle FT, Flames N, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25:10–18PubMedCrossRefGoogle Scholar
  49. 49.
    Stenbeck G (1998) Soluble NSF-attachment proteins. Int J Biochem Cell Biol 30:573–577PubMedCrossRefGoogle Scholar
  50. 50.
    Taupin P (2007) BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation. Brain Res Rev 53:198–214PubMedCrossRefGoogle Scholar
  51. 51.
    Tramontin AD, Garcia-Verdugo JM, Lim DA, Alvarez-Buylla A (2003) Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment. Cereb Cortex 13:580–587PubMedCrossRefGoogle Scholar
  52. 52.
    Valero J, Weruaga E, Murias AR, Porteros A, Alonso JR (2004) Immunodetection of BrdU and PCNA in the rostral migratory stream of the adult mouse. In: Mendez-Vilas A, Labajos-Broncano L (eds) Current issues on multidisciplinary microscopy research and education. FORMATEX, Madrid, pp 118–129Google Scholar
  53. 53.
    Wagner C, Bátiz LF, Rodríguez S et al (2003) Cellular mechanisms involved in the stenosis and obliteration of the cerebral aqueduct of hyh mutant mice developing congenital hydrocephalus. J Neuropathol Exp Neurol 62:1019–1040PubMedGoogle Scholar
  54. 54.
    Woodman PG (1997) The roles of NSF, SNAPs and SNAREs during membrane fusion. Biochim Biophys Acta 1357:155–172PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Luis Federico Bátiz
    • 1
  • Antonio J. Jiménez
    • 2
  • Montserrat Guerra
    • 1
  • Luis Manuel Rodríguez-Pérez
    • 2
  • César D. Toledo
    • 1
  • Karin Vio
    • 1
  • Patricia Páez
    • 2
  • José Manuel Pérez-Fígares
    • 2
  • Esteban M. Rodríguez
    • 1
  1. 1.Instituto de Anatomía, Histología y Patología, Facultad de MedicinaUniversidad Austral de ChileValdiviaChile
  2. 2.Departamento de Biología Celular, Genética y Fisiología, Facultad de CienciasUniversidad de MálagaMálagaSpain

Personalised recommendations