Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation

Cell. 1998 Jan 23;92(2):241-51. doi: 10.1016/s0092-8674(00)80918-6.


The zebrafish one-eyed pinhead (oep) mutation disrupts embryonic development, resulting in cyclopia and defects in endoderm, prechordal plate, and ventral neuroectoderm formation. We report the molecular isolation of oep using a positional cloning approach. The oep gene encodes a novel EGF-related protein with similarity to the EGF-CFC proteins cripto, cryptic, and FRL-1. Wild-type oep protein contains a functional signal sequence and is membrane-associated. Following ubiquitous maternal and zygotic expression, highest levels of oep mRNA are found in the gastrula margin and in axial structures and forebrain. Widespread misexpression of both membrane-attached and secreted forms of oep rescues prechordal plate and forebrain development in mutant embryos but does not lead to the ectopic induction of these cell types in wild-type fish. These results establish an essential but permissive role for an EGF-related ligand during vertebrate gastrulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Cell Membrane / chemistry
  • Central Nervous System / embryology
  • Cloning, Molecular / methods*
  • Endoderm
  • Epidermal Growth Factor / genetics
  • Gastrula / chemistry
  • Gastrula / physiology*
  • Gene Expression Regulation, Developmental
  • Genes / genetics
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • Ligands
  • Molecular Sequence Data
  • Mutation
  • Protein Sorting Signals / genetics
  • RNA, Messenger / analysis
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Transcription Factors / analysis
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • Zebrafish / embryology*
  • Zebrafish / genetics*
  • Zebrafish Proteins*


  • Homeodomain Proteins
  • Ligands
  • Protein Sorting Signals
  • RNA, Messenger
  • Transcription Factors
  • Zebrafish Proteins
  • tdgf1 protein, zebrafish
  • Epidermal Growth Factor

Associated data

  • GENBANK/AF041440
  • GENBANK/AF041441