Epithelial‐Mesenchymal Interactions during Facial Development in Mice

Abstract

Previously, we determined that when avian neural crest cells reach the Frontonasal Process (FNP) at Hamburger and Hamilton Stage 20 (HH), Sonic hedgehog (Shh) expression is induced in the stomodeal ectoderm and forms a boundary with a Fibroblast growth factor 8 (Fgf8) expression domain. The ectoderm flanking this boundary controls FNP growth and patterning, but the mechanisms used by this tissue to pattern the face are unknown. In this work, we examined the facial ectoderm of mice to determine whether a similar signaling center exists and how it functions. Fgf8 is expressed in the distal facial ectoderm at e9.5 and continues to be expressed at e10. At e10 Shh is expressed in both median nasal processes and forms a boundary with Fgf8 in each process. Next, we grafted the mouse ectoderm from e10 embryos onto the dorsal FNP of HH 25 chick embryos. Twenty‐four hours after transplantation the graft (n=4) maintained expression of Fgf8, Shh, Bmp‐2, Bmp‐4, and Bmp‐7, and in the neural crest mesenchyme we observed up‐regulation of Bmp‐4, Bmp‐7, and Msx‐1 and ‐2. By 13 days of development the chimeras exhibited a duplication of the upper beak that was comprised of correctly patterned bone and cartilage (n=4). We observed no hair follicles, but we did observe ectopic egg teeth. These results indicate that in mice a signaling center located in the ectoderm of each median nasal process regulates development of the middle and upper face by inducing signaling molecules that govern skeletogenesis within neural crest mesenchyme. The organization of this center is different from that in the chick where a single Shh domain spans the stomodeal ectoderm and forms a continuous boundary with Fgf8 in the FNP.NIH/NIDCR R01‐1DE018234 to R.M.