Open AccessTranscriptional Profiling of Wnt3a Mutants Identifies Sp Transcription Factors as Essential Effectors of the Wnt/β-catenin Pathway in Neuromesodermal Stem Cells
Author(s) -
William C. Dunty,
Mark W. Kennedy,
Ravindra B. Chalamalasetty,
Kenneth Campbell,
Terry P. Yamaguchi
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0087018
Subject(s) - wnt signaling pathway , effector , biology , wnt3a , stem cell , microbiology and biotechnology , transcription factor , cellular differentiation , neural stem cell , genetics , signal transduction , gene
Neuromesodermal (NM) stem cells reside in the primitive streak (PS) of gastrulating vertebrate embryos and generate precursors of the spinal cord and musculoskeletal system. Although Wnt3a/β-catenin signaling is crucial for NM stem cell maintenance and differentiation, few key transcriptional effectors have been identified. Through a concerted transcriptional profiling and genetic approach we have determined that two Zn 2+ -finger transcription factors, Sp5 and Sp8, are regulated by Wnt3a in the PS, and are essential for neural and musculoskeletal patterning. These results identify Sp5 and Sp8 as pivotal downstream effectors of Wnt3a, and suggest that they are essential for the self-renewal and differentiation of NM stem cells.