The function of the nasal pit in craniofacial morphogenesis

Objective: To test the function of the nasal pit in patterning the upper face. Methods: Avian embryos were used throughout. Loss-of-function experiments consisted of mechanically stripping the right nasal pit using Nile Blue Sulfate. Gain-of-function experiments consisted of grafting donor nasal pits to the side of the head in host embryos. We analysed embryos to look for gene expression changes, morphogenesis of the graft and effects on the beak skeleton. Results: Nasal pits are situated between the lateral nasal and frontonasal mass facial prominences in the upper face. We hypothesized that the nasal pit epithelium patterns the mesenchyme from both of these prominences. We found that extirpation experiments resulted in loss of lateral nasal skeleton but no loss of frontonasal elements. Grafting a supernumerary nasal pit to the maxillary region gave rise to ectopic bone and cartilage. Normally the host maxillary prominence only forms membranous bone. The ectopic skeletal elements were a mixture of maxillary and lateral nasal derivatives. We confirmed that the maxillary mesenchyme had partly converted to a lateral nasal fate by Pax7 antibody staining, a specific lateral nasal marker. The ability of the mesenchyme to respond to supernumerary nasal pits is restricted as the embryo proceeds through development and very little is induced in the oldest hosts tested. An unexpected result was that the nasal pit from E3.5 embryos is able to form neurons and invaginate to form a nasal passage in the ectopic location. Conclusions: The nasal pit provides instructive signals to the lateral nasal mesenchyme to form the nasal conchae and nasal bone. These signals only occur in a lateral direction and do not extend medially to the frontonasal mass.

This work was supported by CIHR operating grants. HSR was supported by the Joseph Tonzetich Fellowship, and JMR by grants from CIHR and MSFHR.