Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts.

Center for Innovative Medicine Karolinska Institutet Huddinge Sweden

Central European Institute of Technology Brno University of Technology Brno Czech Republic

Department of Bioengineering University of Pennsylvania Philadelphia United States

Department of Biosciences and Nutrition Karolinska Institutet Stockholm Sweden

Department of Development Reproduction and Cancer Institute Cochin Paris France

Department of Developmental Biology Institute of Experimental Medicine The Czech Academy of Sciences Prague Czech Republic

Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden

Department of Molecular Neurosciences Medical University Vienna Vienna Austria

Department of Neuroscience and Cell Biology Rutgers Robert Wood Johnson Medical School Piscataway United States

Department of Neuroscience Karolinska Institutet Stockholm Sweden

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

Developmental Biology Unit European Molecular Biology Laboratory Heidelberg Germany

Genomics of Animal Development Unit Institut Pasteur Paris France

Institute for Regenerative Medicine Sechenov 1st Moscow State Medical University Moscow Russia

Institute of Science and Technology IST Austria Klosterneuburg Austria

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