Zebrafish churchill regulates developmental gene expression and cell migration. Issue 6 (29th March 2013)

• Record Type: Journal Article
• Authors: Taibi, Andrew; Mandavawala, Kunal P.; Noel, Justine; Okoye, Ejike V.; Milano, Carolyn R.; Martin, Benjamin L.; Sirotkin, Howard I.
• Is Part Of: Developmental dynamics. Volume 242:Issue 6(2013:Jun.)
• Page Start: 614
• Page End: 621
• Publication Date: 2013-03-29
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.23958
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <underline>Background:</underline> 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. <underline>Results:</underline> We used zinc finger nuclease (ZFN) mediated gene targeting to disrupt the zebrafish <italic>chch</italic> locus and generate the first <italic>chch</italic> 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 <italic>chch</italic> mutants are viable. Mutants have elevated expression of mesodermal markers, but progress normally through early development. <italic>chch</italic> mutants are sensitive to exogenous Nodal. However, neither misregulation of FGF targets nor sensitivity to exogenous FGF was detected. Finally, <italic>chch</italic> mutant cells were found to undergo inappropriate migration in cell transplant assays. <underline>Conclusions:</underline> Together, these results suggest that <italic>chch</italic> is not essential for survival, but functions to modulate early mesendodermal gene expression and limit cell migration. <italic>Developmental Dynamics 242:614–621, 2013</italic>. © 2013 Wiley Periodicals, Inc.†</p> </abstract>