TY - JOUR
T1 - Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling
AU - Kléber, Maurice
AU - Lee, Hye-Youn
AU - Wurdak, Heiko
AU - Buchstaller, Johanna
AU - Riccomagno, Martin M.
AU - Ittner, Lars M.
AU - Suter, Ueli
AU - Epstein, Douglas J.
AU - Sommer, Lukas
PY - 2005/4/25
Y1 - 2005/4/25
N2 - Canonical Wnt signaling instructively promotes sensory neurogenesis in early neural crest stem cells (eNCSCs) (Lee, H.Y., M. Kléber, L. Hari, V. Brault, U. Suter, M.M. Taketo, R. Kemler, and L. Sommer. 2004. Science. 303:1020-1023). However, during normal development Wnt signaling induces a sensory fate only in a subpopulation of eNCSCs while other cells maintain their stem cell features, despite the presence of Wnt activity. Hence, factors counteracting Wnt signaling must exist. Here, we show that bone morphogenic protein (BMP) signaling antagonizes the sensory fate-inducing activity of Wnt/β-catenin. Intriguingly, Wnt and BMP act synergistically to suppress differentiation and to maintain NCSC marker expression and multipotency. Similar to NCSCs in vivo, NCSCs maintained in culture alter their responsiveness to instructive growth factors with time. Thus, stem cell development is regulated by combinatorial growth factor activities that interact with changing cell-intrinsic cues.
AB - Canonical Wnt signaling instructively promotes sensory neurogenesis in early neural crest stem cells (eNCSCs) (Lee, H.Y., M. Kléber, L. Hari, V. Brault, U. Suter, M.M. Taketo, R. Kemler, and L. Sommer. 2004. Science. 303:1020-1023). However, during normal development Wnt signaling induces a sensory fate only in a subpopulation of eNCSCs while other cells maintain their stem cell features, despite the presence of Wnt activity. Hence, factors counteracting Wnt signaling must exist. Here, we show that bone morphogenic protein (BMP) signaling antagonizes the sensory fate-inducing activity of Wnt/β-catenin. Intriguingly, Wnt and BMP act synergistically to suppress differentiation and to maintain NCSC marker expression and multipotency. Similar to NCSCs in vivo, NCSCs maintained in culture alter their responsiveness to instructive growth factors with time. Thus, stem cell development is regulated by combinatorial growth factor activities that interact with changing cell-intrinsic cues.
UR - http://www.scopus.com/inward/record.url?scp=18544390370&partnerID=8YFLogxK
U2 - 10.1083/jcb.200411095
DO - 10.1083/jcb.200411095
M3 - Article
C2 - 15837799
AN - SCOPUS:18544390370
SN - 0021-9525
VL - 169
SP - 309
EP - 320
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -