Transcriptional profiling of Wnt3a mutants identifies Sp transcription factors as essential effectors of the Wnt/β-catenin pathway in neuromesodermal stem cells.
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.
Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, United States of America.
William C
WC
Dunty
Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, United States of America.
Mark W L
MW
Kennedy
Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, United States of America.
Ravindra B
RB
Chalamalasetty
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Kenneth
K
Campbell
Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, United States of America.
Terry P
TP
Yamaguchi
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D054262:Gastrulation / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D054240:Primitive Streak / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D060509:Wnt3A Protein / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D004268:DNA-Binding Proteins; C417217:Sp5 protein, mouse; C490035:Sp8 protein, mouse; D014157:Transcription Factors; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin