Alexander, C., Zuniga, E., Blitz, I.L., Wada, N., Le Pabic, P., Javidan, Y., Zhang, T., Cho, K.W., Crump, J.G., and Schilling, T.F. (2011) Combinatorial roles for BMPs and Endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton. Development (Cambridge, England). 138(23):5135-5146.
Bone morphogenetic proteins (BMPs) play crucial roles in craniofacial development but little is known about their interactions
with other signals, such as Endothelin 1 (Edn1) and Jagged/Notch, which pattern the dorsal-ventral (DV) axis of the pharyngeal
arches. Here, we use transgenic zebrafish to monitor and perturb BMP signaling during arch formation. With a BMP-responsive
transgene, Tg(Bre:GFP), we show active BMP signaling in neural crest (NC)-derived skeletal precursors of the ventral arches, and in surrounding epithelia.
Loss-of-function studies using a heat shock-inducible, dominant-negative BMP receptor 1a [Tg(hs70I:dnBmpr1a-GFP)] to bypass early roles show that BMP signaling is required for ventral arch development just after NC migration, the same
stages at which we detect Tg(Bre:GFP). Inhibition of BMP signaling at these stages reduces expression of the ventral signal Edn1, as well as ventral-specific genes
such as hand2 and dlx6a in the arches, and expands expression of the dorsal signal jag1b. This results in a loss or reduction of ventral and intermediate skeletal elements and a mis-shapen dorsal arch skeleton.
Conversely, ectopic BMP causes dorsal expansion of ventral-specific gene expression and corresponding reductions/transformations
of dorsal cartilages. Soon after NC migration, BMP is required to induce Edn1 and overexpression of either signal partially
rescues ventral skeletal defects in embryos deficient for the other. However, once arch primordia are established the effects
of BMPs become restricted to more ventral and anterior (palate) domains, which do not depend on Edn1. This suggests that BMPs
act upstream and in parallel to Edn1 to promote ventral fates in the arches during early DV patterning, but later acquire
distinct roles that further subdivide the identities of NC cells to pattern the craniofacial skeleton.