Sequential actions of BMP receptors control neural precursor cell production and fate

Bone morphogenetic proteins (BMPs) have diverse and sometimes paradoxical e ffects during embryonic development. To determine the mechanisms underlying BMP actions, we analyzed the expression and function of two BMP receptors, BMPR-IA and BMPR-IB, in neural precursor cells in vitro and in vivo. Neura l precursor cells always express Bmpr-1a, but Bmpr-1b is not expressed unti l embryonic day 9 and is restricted to the dorsal neural tube surrounding t he source of BMP ligands. BMPR-IA activation induces (and Sonic hedgehog pr events) expression of Rmpr-1b along with dorsal identity genes in precursor cells and promotes their proliferation. When BMPR-IB is activated, it limi ts precursor cell numbers by causing mitotic arrest. This results in apopto sis in early gestation embryos and terminal differentiation in mid-gestatio n embryos. Thus, BMP actions are first inducing (through BMPR-IA) and then terminating (through BMPR-IB), based on the accumulation of BMPR-IB relativ e to BMPR-IA. We describe a feed-forward mechanism to explain how the seque ntial actions of these receptors control the production and fate of dorsal precursor cells from neural stem cells.