Quantitative analyses link modulation of sonic hedgehog signaling to continuous variation in facial growth and shape.
Variation is an intrinsic feature of biological systems, yet developmental biology does not frequently address population-level phenomena. Sonic hedgehog (SHH) signaling activity in the vertebrate forebrain and face is thought to contribute to continuous variation in the morphology of the upper jaw, but despite its potential explanatory power, this idea has never been quantitatively assessed. Here, we test this hypothesis with an experimental design that is explicitly focused on the generation and measurement of variation in multivariate shape, tissue growth, cellular behavior and gene expression. We show that the majority of upper jaw shape variation can be explained by progressive changes in the spatial organization and mitotic activity of midfacial growth zones controlled by SHH signaling. In addition, nonlinearity between our treatment doses and phenotypic outcomes suggests that threshold effects in SHH signaling may play a role in variability in midfacial malformations such as holoprosencephaly (HPE). Together, these results provide novel insight into the generation of facial morphology, and demonstrate the value of quantifying variation for our understanding of development and disease.
Young
Nathan M
NM
Department of Orthopaedic Surgery, University of California-San Francisco, 2550 23rd Street, San Francisco, CA 94110, USA.
Chong
H Jonathan
HJ
Hu
Diane
D
Hallgrímsson
Benedikt
B
Marcucio
Ralph S
RS
D000818:Animals; D001837:Body Weights and Measures; D049109:Cell Proliferation; D002642:Chick Embryo; D017931:DNA Primers / Q000235:genetics; D005147:Facial Bones / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D053823:Hedgehog Proteins
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