Evolution of the gene regulatory network for pharyngeal segmentation

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The bones and cartilages of the jaws, face, neck, and inner ear develop from embryonic structures called pharyngeal arches. Defects in pharyngeal arch development underlie many human birth defects. The pharyngeal arches of non-human vertebrates also form most of the head skeleton, including the gills of aquatic vertebrates. Though the pharyngeal arches form similarly in all vertebrates, they ultimately give rise very different head skeletons in different vertebrate groups. How such variation is achieved using the same basic set of genes and developmental processes is unclear. The project seeks to elucidate the aspects of pharyngeal arch development shared by all vertebrates, and those that differ between major groups. This information will serve two purposes. First, it will shed light on the genetic and developmental changes that led to the evolution of new vertebrate groups. Second, it will help identify the causes of genetic and environmentally-induced disruptions human craniofacial development. This project will also support the creation and staffing of a large, interactive zoo exhibit entitled “Hidden Links: Discovering Your Inner Invertebrate”, that will be seen by over 300,000 visitors annually, including 57,000 grade school students. The exhibit will expose visitors to key biological concepts such as evolution, phylogenetics, genetics, segmentation, and development. The work will also support the training of three Ph.D. students, several undergraduates, and provide research projects for 1-2 high school students per year.Robust, paired pharyngeal arches (PAs) are a defining feature of vertebrates. PAs form most of the breathing and feeding structures of the vertebrate “new head”, and variation in PA number and derivatives is a major contributor to vertebrate morphological diversity. Though PAs play a key role in shaping the vertebrate head, the genetic mechanisms driving PA development are poorly understood. Even less is known about how they have been altered during evolution to yield different oropharyngeal phenotypes. The PAs form in an anterior-to-posterior sequence when bilateral endodermal outpocketings called pharyngeal pouches (PPs) contact overlying ectoderm. Studies in zebrafish, medaka, and mouse have identified a small, conserved set of genes that drives PP development in model vertebrates. However, how these genes interact differs between teleosts and mouse. When during evolution these gene regulatory differences arose, and if they contribute to differences in oropharyngeal morphology, is unknown. To better understand the genetic bases of vertebrate oropharyngeal diversity, this work will reconstruct the ancestral gene regulatory network for PP/PA development (the PP GRN). This information will then be used to deduce how and why the PP GRN has been altered in modern lineages. To do this, the PP GRN of the sea lamprey, Petromyzon marinus, and the frog, Xenopus laevis will be interrogated using CRISPR/Cas9 mutagenesis and pharmacological perturbations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.