Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure

Ezequiel J. Tolosa, Martin E Fernandez-Zapico, Natalia L. Battiato, Roberto A. Rovasio

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Our aim was to understand the involvement of Sonic hedgehog (Shh) morphogen in the oriented distribution of neural crest cells (NCCs) toward the optic vesicle and to look for potential disorders of this guiding mechanism after ethanol exposure.In vitro directional analysis showed the chemotactic response of NCCs up Shh gradients and to notochord co-cultures (Shh source) or to their conditioned medium, a response inhibited by anti-Shh antibody, receptor inhibitor cyclopamine and anti-Smo morpholino (MO). Expression of the Ptch-Smo receptor complex on in vitro NCCs was also shown. In whole embryos, the expression of Shh mRNA and protein was seen in the ocular region, and of Ptch, Smo and Gli/Sufu system on cephalic NCCs. Anti-Smo MO or Ptch-mutated plasmid (Ptch1δloop2) impaired cephalic NCC migration/distribution, with fewer cells invading the optic region and with higher cell density at the homolateral mesencephalic level. Beads embedded with cyclopamine (Smo-blocking) or Shh (ectopic signal) supported the role of Shh as an in vivo guide molecule for cephalic NCCs.Ethanol exposure perturbed in vitro and in vivo NCC migration. Early stage embryos treated with ethanol, in a model reproducing Fetal Alcohol Syndrome, showed later disruptions of craniofacial development associated with abnormal in situ expression of Shh morphogen.The results show the Shh/Ptch/Smo-dependent migration of NCCs toward the optic vesicle, with the support of specific inactivation with genetic and pharmacological tools. They also help to understand mechanisms of accurate distribution of embryonic cells and of their perturbation by a commonly consumed teratogen, and demonstrate, in addition to its other known developmental functions, a new biological activity of cellular guidance for Shh.

Original languageEnglish (US)
JournalEuropean Journal of Cell Biology
DOIs
StateAccepted/In press - Jun 20 2015

Fingerprint

Neural Crest
Ethanol
Morpholinos
Head
Cell Movement
Embryonic Structures
Hedgehog Proteins
Teratogens
Notochord
Fetal Alcohol Spectrum Disorders
Conditioned Culture Medium
Coculture Techniques
Plasmids
Cell Count
Pharmacology
Messenger RNA
Antibodies

Keywords

  • Cell guiding
  • Cell migration
  • Chemotaxis
  • Chick embryo
  • Ethanol
  • Neural crest cells
  • Sonic hedgehog

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine

Cite this

Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure. / Tolosa, Ezequiel J.; Fernandez-Zapico, Martin E; Battiato, Natalia L.; Rovasio, Roberto A.

In: European Journal of Cell Biology, 20.06.2015.

Research output: Contribution to journalArticle

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