title: Sonic hedgehog (Shh)/Gli modulates the spatial organization of neuroepithelial cell proliferation in the developing chick optic tectum.
abstract: BACKGROUND
  Sonic hedgehog (Shh)/Gli pathway plays an important regulatory role on the neuroepithelial cells (NEc) proliferation in the dorsal regions of the developing vertebrate Central Nervous System. The aim of this paper was to analyze the effect of the Shh/Gli signaling pathway activation on the proliferation dynamics and/or the spatial organization of the NEc proliferation activity during early stages of the developing chick optic tectum (OT). In ovo pharmacological gain and loss of hedgehog function approaches were complemented with in vivo electroporation experiments in order to create ectopic sources of either Shh or Gli activator (GliA) proteins in the OT. NEc proliferating activity was analyzed at ED 4/4.5 by recording the spatial co-ordinates of the entire population of mitotic NEc (mNEc) located along OT dorsal-ventral sections. Several space signals (numerical sequences) were derived from the mNEc spatial co-ordinate records and analyzed by different standardized non-linear methods of signal analysis.
  
  
  RESULTS
  In ovo pharmacologic treatment with cyclopamine resulted in dramatic failure in the OT expansion while the agonist purmorphamine produced the opposite result, a huge expansion of the OT vesicle. Besides, GliA and Shh misexpressions interfere with the formation of the intertectal fissure located along the dorsal midline. This morphogenetic alteration is accompanied by an increase in the mNEc density. There is a gradient in the response of NEcs to Shh and GliA: the increase in mNEc density is maximal near the dorsal regions and decrease towards the OT-tegmental boundary. Biomathematical analyses of the signals derived from the mNEc records show that both Shh and GliA electroporations change the proliferation dynamics and the spatial organization of the mNEc as revealed by the changes in the scaling index estimated by these methods.
  
  
  CONCLUSIONS
  The present results show that the Shh/Gli signaling pathway plays a critical role in the OT expansion and modelling. This effect is probably mediated by a differential mitogenic effect that increases the NEc proliferation and modulates the spatial organization of the NEc proliferation activity.
authors.affiliation: Interdisciplinary Group in Theoretical Biology, Department Biostructural Sciences, Favaloro University, Solís 453 (1078), Buenos Aires, Argentina.
authors.forename: Melina
authors.initials: M
authors.lastname: Rapacioli
authors.forename: Joao
authors.initials: J
authors.lastname: Botelho
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cerda
authors.forename: Santiago
authors.initials: S
authors.lastname: Duarte
authors.forename: Matías
authors.initials: M
authors.lastname: Elliot
authors.forename: Verónica
authors.initials: V
authors.lastname: Palma
authors.forename: Vladimir
authors.initials: V
authors.lastname: Flores
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002642:Chick Embryo; D018274:Electroporation / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D053823:Hedgehog Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D046569:Neuroepithelial Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D015513:Oncogene Proteins / Q000502:physiology*; D011687:Purines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013477:Superior Colliculi / Q000033:anatomy & histology* / Q000187:drug effects / Q000254:growth & development; D013723:Teratogens / Q000494:pharmacology; D015534:Trans-Activators / Q000502:physiology*; D014704:Veratrum Alkaloids / Q000494:pharmacology; D000071676:Zinc Finger Protein GLI1
chemical_list: D053823:Hedgehog Proteins; D009025:Morpholines; D015513:Oncogene Proteins; D011687:Purines; D013723:Teratogens; D015534:Trans-Activators; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C470893:purmorphamine; C000541:cyclopamine