Meeting Abstract
Variation is the key element of biological populations that natural selection works upon to produce evolutionary change. Sonic hedgehog (SHH) signaling variation has been implicated in major evolutionary transformations in craniofacial morphology, including between avians and mammals, and between cavefish populations. In humans, mutations in SHH and in other members of the SHH signaling pathway have been linked to the disease holoprosencephaly (HPE). HPE phenotypes range broadly from mild midfacial narrowing to cyclopia, but it remains unknown what causes this broad range. Our lab has collected data suggesting that the relationship between SHH-signaling and facial morphology appears to be non-linear. We are determining whether modulating the cellular reception of SHH will produce a continuous spectrum of facial phenotypes by producing an allelic series of mouse embryos with discrete, genetic reductions in both the cell’s ability to respond to SHH (via loss of functional alleles for the endocytic receptor LRP2) and in the amount of ligand available (via loss of functional SHH alleles). We used geometric morphometric analysis to quantify craniofacial shape variation, and used TUNEL and immunohistochemistry to examine cell death and proliferation, respectively. Our preliminary data indicate that the greatest differences in craniofacial shape exist between SHH+/-; LRP2+/- embryos, and embryos with loss of either a single SHH or LRP2 allele or wild type embryos. Examining how small changes in SHH signaling produce morphological variation will better our understanding of not only human disease, but also of macroevolutionary changes in morphologies dependent on SHH signaling.
