CDB Seminar - Prof Matthew Harris, Harvard Medical School, Boston Children’s Hospital

Talk abstract: Though our anatomy has been refined and shaped by evolution, we all, in an evolutionary sense, share core developmental mechanisms with the earliest jawed fish that swam in distant oceans. These historical rudiments can be seen in the conservation of general patterning mechanisms such as the formation of homologous structures and forms across the 530 million years of vertebrate evolution. The jaw is one of the first novel skeletal structures to form and led to the expansion of gnathostomes (jawed vertebrates) including us. In nature, jaws come in myriad sizes and shapes. My lab leverages such natural variation to look across evolution to map out changes in the genetic instructions that lead to variation in form. In studying how differential proportion arises in needlefish and halfbeaks - a clade of fish with an impressive expansion of length of the frontonasal skeleton - we identified core pathways that also associate with microsomia and micrognathia in humans. The changes we define highlight a highly conserved regulatory ‘hub’ that specifically controls gene function in a select population of neural-crest derived cartilage cells. These cells look like, and behave like cartilage, but do not share common cartilage genes or defining components. Thus, these cells have never been defined as a component of the craniofacial complex. We find these cells have a unique morphogenesis patterns and developmental sequence, but do not directly participate in the early patterning of the craniofacial complex – rather they look to stabilize as cartilage structures, making unique and new skeletal elements when development is shifted. As such these previously undefined cells seem to be ‘set aside’ from normal skeletal components, acting as a reservoir for skeletal material in the case of change. Supporting this, the extended jaws of needlefish and halfbeak are derived from structures that mirror position and type of such set aside cells, forming a novel toothless extension of weakly staining cartilage rods.  We know these cells participate in formation of the human jaw and are linked to dysmorphology in patients.  Leveraging their plasticity may provide unique insights into repair and plasticity of the jaw and dentary as well as evolutionary history of the jaw.

Host: Ale Mongera