Zebrafish sip1a and sip1b are essential for normal axial and neural patterning

Dev Dyn. 2008 Apr;237(4):1060-9. doi: 10.1002/dvdy.21485.


Smad-interacting protein-1 (SIP1) has been implicated in the development of Mowat-Wilson syndrome whose patients exhibit Hirschsprung disease, an aganglionosis of the large intestine, as well as other phenotypes. We have identified and cloned two sip1 orthologues in zebrafish. Both sip1 orthologues are expressed maternally and have dynamic zygotic expression patterns that are temporally and spatially distinct. We have investigated the function of both orthologues using translation and splice-blocking morpholino antisense oligonucleotides. Knockdown of the orthologues causes axial and neural patterning defects consistent with the previously described function of SIP1 as an inhibitor of BMP signaling. In addition, knockdown of both genes leads to a significant reduction/loss of the post-otic cranial neural crest. This results in a subsequent absence of neural crest precursors in the posterior pharyngeal arches and a loss of enteric precursors in the intestine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Humans
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Morphogenesis
  • Neural Crest / cytology
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Phenotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Stem Cells / physiology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*
  • Zebrafish* / anatomy & histology
  • Zebrafish* / embryology
  • Zebrafish* / metabolism


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Oligonucleotides, Antisense
  • Protein Isoforms
  • Zebrafish Proteins
  • gemin2 protein, zebrafish