BMP-7 influences pattern and growth of the developing hindbrain of mouse embryos

Abstract

The expression pattern of bone morphogenetic protein-7 (BMP-7) in the hindbrain region of the headfold and early somite stage developing mouse embryo suggests a role for BMP-7 in the patterning of this part of the cranial CNS. In chick embryos it is thought that BMP-7 is one of the secreted molecules which mediates the dorsalizing influence of surface ectoderm on the neural tube, and mouse surface ectoderm has been shown to have a similar dorsalizing effect. While we confirm that BMP-7 is expressed in the surface ectoderm of mouse embryos at the appropriate time to dorsalize the neural tube, we also show that at early stages of hindbrain development BMP-7 transcripts are present in paraxial and ventral tissues, within and surrounding the hindbrain neurectoderm, and only later does expression become restricted to a dorsal domain. To determine more directly the effect that BMP-7 may have on the developing hindbrain we have grafted COS cells expressing BMP-7 into the ventrolateral mesoderm abutting the neurectoderm in order to prolong BMP-7 expression in the vicinity of ventral hindbrain. Three distinct actvities of BMP-7 are apparent. Firstly, as expected from previous work in chick, BMP-7 can promote dorsal characteristics in the neural tube. Secondly, we show that it can also attenuate the expression of sonic hedgehog (Shh) in the floorplate without affecting Shh expression in the notochord. Finally, we find that ectopic BMP-7 appears to promote growth of the neurectoderm. These findings are discussed with respect to possible timing mechanisms necessary for the coordination of hindbrain dorsoventral patterning.