title: Asymmetric Wnt Pathway Signaling Facilitates Stem Cell-Like Divisions via the Nonreceptor Tyrosine Kinase FRK-1 in Caenorhabditis elegans.
abstract: Asymmetric cell division is critical during development, as it influences processes such as cell fate specification and cell migration. We have characterized FRK-1, a homolog of the mammalian Fer nonreceptor tyrosine kinase, and found it to be required for differentiation and maintenance of epithelial cell types, including the stem cell-like seam cells of the hypodermis. A genomic knockout of frk-1, allele ok760, results in severely uncoordinated larvae that arrest at the L1 stage and have an excess number of lateral hypodermal cells that appear to have lost asymmetry in the stem cell-like divisions of the seam cell lineage. frk-1(ok760) mutants show that there are excess lateral hypodermal cells that are abnormally shaped and smaller in size compared to wild type, a defect that could be rescued only in a manner dependent on the kinase activity of FRK-1. Additionally, we observed a significant change in the expression of heterochronic regulators in frk-1(ok760) mutants. However, frk-1(ok760) mutants do not express late, nonseam hypodermal GFP markers, suggesting the seam cells do not precociously differentiate as adult-hyp7 cells. Finally, our data also demonstrate a clear role for FRK-1 in seam cell proliferation, as eliminating FRK-1 during the L3-L4 transition results in supernumerary seam cell nuclei that are dependent on asymmetric Wnt signaling. Specifically, we observe aberrant POP-1 and WRM-1 localization that is dependent on the presence of FRK-1 and APR-1. Overall, our data suggest a requirement for FRK-1 in maintaining the identity and proliferation of seam cells primarily through an interaction with the asymmetric Wnt pathway.
authors.affiliation: Department of Biology, Hope Colloge, Holland, Michigan 49423.
authors.forename: Danielle
authors.initials: D
authors.lastname: Mila
authors.affiliation: Department of Biology, Hope College, Holland, Michigan 49423.
authors.forename: Adriana
authors.initials: A
authors.lastname: Calderon
authors.affiliation: Department of Biology, University of Iowa, Iowa City, Iowa 52242-1324.
authors.forename: Austin T
authors.initials: AT
authors.lastname: Baldwin
authors.affiliation: Department of Biology, Hope Colloge, Holland, Michigan 49423.
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Moore
authors.affiliation: Department of Biology, Hope Colloge, Holland, Michigan 49423.
authors.forename: McLane
authors.initials: M
authors.lastname: Watson
authors.affiliation: Department of Biology, University of Iowa, Iowa City, Iowa 52242-1324.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Phillips
authors.affiliation: Department of Biology, Hope College, Holland, Michigan 49423 aputzke@whitworth.edu.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Putzke
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology; D055786:Gene Knockout Techniques; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D029742:Caenorhabditis elegans Proteins; D011505:Protein-Tyrosine Kinases; C503592:FRK-1 protein, C elegans
keywords: Wnt; asymmetry; development; fer; kinase