The Non‐Canonical Wnt/Calcium Pathway Regulates the Migration and Function of Primary Mesenchyme Cells

Abstract

The highly conserved non‐canonical Wnt/Calcium Signaling Pathway (ncWnt/Ca2+) has been shown to regulate cell motility and epithelial to mesenchymal transition, implicating its role in various developmental processes and cancer invasiveness. We use the sea urchin Primary Mesenchyme Cells (PMCs), the only skeletogenic cells in developing sea urchin embryos, to examine directed cell migration. The working hypothesis is that PMC migration and PMC skeletal function are in part regulated by the ncWnt/Ca2+ signaling pathway. We have shown that disruption of elements downstream of the ncWnt/Ca2+ pathway using perturbative drugs decreased embryonic skeletal length as well as dramatically altered PMC migration patterns. In addition to producing similar skeletal and migratory defects, activation of Protein Kinase C (PKC) downstream of the ncWnt/Ca2+ pathway by Phorbol 12‐myristate 13‐acetate (PMA) also resulted in altered spatial expression of transcripts known to regulate PMC migration and function, as well as changed the expression levels of biomineralization genes. Similar phenotypes were observed in PMA treated embryos and the microRNA‐1 (miR‐1) knockdown embryos. MicroRNAs (miRNAs) are short, non‐coding RNAs that suppress gene expression by binding to the 3′UTR of target mRNA transcripts to repress translation. MiR‐1 is bioinformatically identified to bind to PKC and cdc42 of the ncWnt/Ca2+ signaling cascade, indicating its potential role in regulating the ncWnt/Ca2+ signaling pathway. This study identifies the molecular mechanisms of how the ncWnt/Ca2+ pathway impacts PMC directed migration and developmental function which may potentially contribute to our understanding of birth defects and cancer metastasis.Support or Funding Information ‐Senior Thesis Winter Session Scholars Award (Fall 2017) ‐Undergraduate Research Supplies‐And‐Expense Grant (Fall 2016, Fall 2017) ‐Science and Engineering Summer Scholar Award (Summer 2017) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.