title: Zebrafish churchill regulates developmental gene expression and cell migration.
abstract: BACKGROUND
  Regulation of developmental signaling pathways is essential for embryogenesis. The small putative zinc finger protein, Churchill (ChCh) has been implicated in modulation of both TGF-β and FGF signaling.
  
  
  RESULTS
  We used zinc finger nuclease (ZFN) mediated gene targeting to disrupt the zebrafish chch locus and generate the first chch mutations. Three induced lesions produce frameshift mutations that truncate the protein in the third of five β-strands that comprise the protein. Surprisingly, zygotic and maternal zygotic chch mutants are viable. Mutants have elevated expression of mesodermal markers, but progress normally through early development. chch mutants are sensitive to exogenous Nodal. However, neither misregulation of FGF targets nor sensitivity to exogenous FGF was detected. Finally, chch mutant cells were found to undergo inappropriate migration in cell transplant assays.
  
  
  CONCLUSIONS
  Together, these results suggest that chch is not essential for survival, but functions to modulate early mesendodermal gene expression and limit cell migration.
authors: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York.
authors: Andrew
authors: A
authors: Taibi
authors: Kunal P
authors: KP
authors: Mandavawala
authors: Justine
authors: J
authors: Noel
authors: Ejike V
authors: EV
authors: Okoye
authors: Carolyn R
authors: CR
authors: Milano
authors: Benjamin L
authors: BL
authors: Martin
authors: Howard I
authors: HI
authors: Sirotkin
mesh_terms: D000483:Alleles; D000818:Animals; D019521:Body Patterning; D002465:Cell Movement; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D009154:Mutation; D055457:Nodal Protein / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019076:Transgenes; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: C480345:CHURC1 protein, Xenopus; D055457:Nodal Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C526742:churc1 protein, zebrafish; D005346:Fibroblast Growth Factors