ZFIN ID: ZDB-PUB-110512-18
Development of Extraocular Muscles Require Early Signals From Periocular Neural Crest and the Developing Eye
Bohnsack, B.L., Gallina, D., Thompson, H., Kasprick, D.S., Lucarelli, M.J., Dootz, G., Nelson, C., McGonnell, I.M., and Kahana, A.
Date: 2011
Source: Archives of ophthalmology (Chicago, Ill. : 1960)   129(8): 1030-1041 (Journal)
Registered Authors: Bohnsack, Brenda, Kahana, Alon, Kasprick, Dan, McGonnell, Imelda
Keywords: none
MeSH Terms:
  • Animals
  • Anophthalmos/genetics
  • Anophthalmos/pathology
  • Cell Differentiation
  • Chick Embryo
  • Child, Preschool
  • Eye Enucleation
  • Homeodomain Proteins/genetics
  • Humans
  • In Situ Hybridization
  • Infant
  • Magnetic Resonance Imaging
  • Morphogenesis
  • Myosin Heavy Chains/genetics
  • Neural Crest/embryology*
  • Neural Crest/metabolism
  • Neural Crest/pathology
  • Oculomotor Muscles/embryology*
  • Oculomotor Muscles/metabolism
  • Oculomotor Muscles/pathology
  • Orbit/embryology*
  • Orbit/pathology
  • Receptors, Retinoic Acid/genetics
  • Retrospective Studies
  • Signal Transduction/physiology*
  • Time Factors
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics
PubMed: 21482859 Full text @ Arch. Ophthalmol.


To identify and explain morphologic changes of the extraocular muscles (EOMs) in anophthalmic patients.


Retrospective medical record review of patients with congenital anophthalmia, using magnetic resonance imaging and intraoperative findings to characterize EOM morphology. We then used molecular biology techniques in zebrafish and chick embryos to determine the relationships among the developing eye, periocular neural crest, and EOMs.


In 3 human patients with bilateral congenital anophthalmia and preoperative orbital imaging, we observed a spectrum of EOM morphologies ranging from indiscernible muscle tissue to well-formed, organized EOMs. Timing of eye loss in zebrafish and chick embryos correlated with the morphology of EOM organization in the orbit (eye socket). In congenitally eyeless Rx3 zebrafish mutants, or following genetic ablation of the cranial neural crest cells, EOMs failed to organize, which was independent of other craniofacial muscle development.


Orbital development is dependent on interactions between the eye, neural crest, and developing EOMs. Timing of the ocular insult in relation to neural crest migration and EOM development is a key determinant of aberrant EOM organization. Additional research will be required to study patients with unilateral and syndromic anophthalmia and assess for possible differences in clinical outcomes of patients with varied EOM morphology. Clinical Relevance  The presence and organization of EOMs in anophthalmic eye sockets may serve as a markers for the timing of genetic or teratogenic insults, improving genetic counseling, and assisting with surgical reconstruction and family counseling efforts.