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Updated: Feb 7, 2026

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
A conserved C. elegans zinc finger-homeodomain protein, ZFH-2, continuously required for structural integrity and
Antoine Sussfeld1, Berta Vidal1, Surojit Sural1
1Columbia University, Department of Biological Sciences, Howard Hughes Medical Institute, New York, NY 10027.
Abstract:
An unusually large transcription factor arose at the base of bilaterian evolution through domain shuffling that recombined many copies of two distinct DNA binding domains, C2H2-type zinc fingers and homeodomains. The function of this deeply conserved type of protein remains poorly characterized. We describe here the complete and complex expression pattern of its sole C. elegans representative, ZFH-2, throughout development and adulthood. We show that animals lacking this protein display defects in proper alimentary tract formation and starve to death in the first larval stage with an apparent inability to ingest food. Conditional removal of ZFH-2 at post-developmental stages reveals a continuous function of this protein in enabling food ingestion and demonstrates additional essential functions for the formation of other, postembryonically generated tubular structures. Even though ZFH-2 is broadly expressed throughout the nervous system, we detected no obvious defects in neuronal development or function in zfh-2 null mutants. Genome-engineered alleles indicate that while a large part of the protein is dispensable, at least a subset of the homeodomains are critical determinants for the essential functions of this protein.
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