Alternative Neural Crest Cell Fates Are Instructively Promoted by TGFβ Superfamily Members
How growth factors influence the fate of multipotent progenitor cells is not well understood. Most hematopoietic growth factors act selectively as survival factors, rather than instructively as lineage determination signals. In the neural crest, neuregulin instructively promotes gliogenesis, but how alternative fates are determined is unclear. We demonstrate that bone morphogenic protein 2 (BMP2) induces the basic–helix-loop-helix protein MASH1 and neurogenesis in neural crest stem cells. In vivo, MASH1^+ cells are located near sites of BMP2 mRNA expression. Some smooth muscle differentiation is also observed in BMP2. A related factor, transforming growth factor β1 (TGFβ1), exclusively promotes smooth muscle differentiation. Like neuregulin, BMP2 and TGFβ1 act instructively rather than selectively. The neural crest and hematopoietic systems may therefore utilize growth factors in different ways to generate cellular diversity.
© 1996 Cell Press. Under an Elsevier user license. Received January 18, 1996; Revised March 14, 1996. We thank Brigid Hogan for providing BMP2 and BMP4 probes; Victor Koteliansky for advice on smooth muscle markers and for antibodies; Chrees Schoenherr for suggesting the use of αSMA; Derek Stemple for help with some of the experiments; and Barbara Wold, Scott Fraser, Kai Zinn, Derek Stemple, Tom Clandinin, Lukas Sommer, Richard Axel, and Tom Jessell for their comments on the manuscript. D. J. A. is an Associate Investigator of the Howard Hughes Medical Institute. This work was supported in part by National Institutes of Health grant NS23476.