title: Cell death and cell proliferation in human spina bifida.
abstract: BACKGROUND
  Spina bifida is a multifactorial congenital malformation of the central nervous system. The aim of this study was to ascertain the relevance of cell death/proliferation balance in human spina bifida and to assess autophagy distribution and levels during embryo-fetal development in neural tissue.
  
  
  METHODS
  Five human cases with myelomeningocoele were compared with 10 healthy human controls and LC3 protein expression was also analyzed in mouse embryos. Cell death was evaluated using TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling) assay; cell proliferation was studied by counting Ki67-positive cells, and autophagy was assessed by observing the presence of LC3 punctuate dots.
  
  
  RESULTS
  Comparing human cases and controls (13 to 21 weeks of gestation), we observed a significant increase in TUNEL-positive cells in human spina bifida associated with a significantly decreased proliferation rate, indicating an alteration of the physiological cell rate homeostasis. LC3 distribution was found to be spatiotemporally regulated in both human and murine embryo-fetuses: in early pregnancy a diffuse and ubiquitous LC3 signal was detected. After neural tube closure, an intense LC3-positive signal, normally associated to extra energy requirement, was confined to the Lissauer's tract, the dorsolateral spinal zone containing centrally projecting axons from dorsal root ganglia, at any medullar levels. LC3 signal disappeared from 12 weeks of gestation.
  
  
  CONCLUSIONS
  In conclusion, this study confirms the fundamental role of cell death/proliferation balance during central nervous system development and reports the changing expression of LC3 protein in mouse and human neural tube. Birth Defects Research (Part A) 106:104-113, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Università degli studi di Milano, Dipartimento di Scienze della Salute, Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Avagliano
authors.affiliation: Università degli studi di Milano, Dipartimento di Scienze della Salute, Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Doi
authors.affiliation: Università degli studi di Milano, Dipartimento di Scienze della Salute, Milano, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Tosi
authors.affiliation: Centre for Endocrinology, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, Charter House Square, London, United Kingdom.
authors.forename: Valeria
authors.initials: V
authors.lastname: Scagliotti
authors.affiliation: Centre for Endocrinology, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, Charter House Square, London, United Kingdom.
authors.forename: Angelica
authors.initials: A
authors.lastname: Gualtieri
authors.affiliation: Centre for Endocrinology, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, Charter House Square, London, United Kingdom.
authors.forename: Carles
authors.initials: C
authors.lastname: Gaston-Massuet
authors.affiliation: Università degli Studi di Milano, Dip. Biotecnologie Mediche e Medicina Traslazionale, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pistocchi
authors.affiliation: Università degli studi di Milano, Dipartimento di Scienze della Salute, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallina
authors.affiliation: Università degli studi di Milano, Dipartimento di Scienze della Salute, Milano, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Marconi
authors.affiliation: Università degli studi di Milano, Dipartimento di Scienze della Salute, Milano, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bulfamante
authors.affiliation: Università degli studi di Milano, Dipartimento di Scienze della Salute, Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Massa
mesh_terms: D000328:Adult; D000818:Animals; D001343:Autophagy; D016022:Case-Control Studies; D016923:Cell Death; D049109:Cell Proliferation; D005260:Female; D005865:Gestational Age; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008591:Meningomyelocele / Q000196:embryology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D054259:Neural Tube / Q000196:embryology* / Q000473:pathology; D011247:Pregnancy; D016135:Spinal Dysraphism / Q000196:embryology*
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins
keywords: LC3; Lissauer's tract; autophagy; cell death/proliferation; neural tube defects