CAREER: Functional Analysis of Crest EffectorS in Craniofacial Development

University Of California-Davis, Davis CA

Investigators

Abstract

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117- 2). A long-standing question in the fields of developmental and evolutionary biology is to understand how animals develop different outer appearances using similar genetic programs. The goal of this project is to enhance our knowledge of how embryonic neural crest stem cells form the tissues that make the face in closely related organisms, and how these stem cells give rise distinct outer appearances. To achieve this goal, Dr. Rogers at UC Davis will work with undergraduate students to dissect the programs that regulate the formation of neural crest cells in three bird species. The dual research and educational project called Functional Analysis of Crest EffectorS (FACES), will identify how changing the expression of these proteins at early embryonic stages drives differences in beak structure in quail, chicken, and peafowl embryos. Dr. Rogers has a strong background in studying neural crest cells and early development across various species, and is one of the few investigators in the world performing cross-species analyses to define the molecular control of cell specification and cell migration in avians. This faculty Early Career Development Award (CAREER) will fund a research and educational program that provides professional growth, hands-on research opportunities and long-term mentoring for undergraduate students, and will increase our fundamental understanding of how complex tissues are formed during vertebrate embryonic development. By asking the question, “what regulates the cells that make the face?” we can unravel the mechanisms driving formation of faces in different species. Much of the information we know about neural crest development has been identified independently in a handful of model organisms, and the findings have been incorporated into a neural crest gene regulatory network model to resolve protein-gene interactions. However, we lack confirmation of the functional conservation of proteins across species, thereby making comprehensive understanding of neural crest evolution and development challenging. Although the expression of the factors that regulate neural crest development are conserved, we do not know if they function at the same developmental time, regulate the same targets, or if changes in these factors drive phenotypic variation across species. This CAREER will directly address this barrier to knowledge by defining the roles of three SOXE (SRY-related HMG box Group E) transcription factors, and their putative targets, type I and II cadherin molecules, in the formation of neural crest cells and their craniofacial derivatives. Quail, chick, and peafowl embryos will be used to compare expression timing, protein function, and outcome of protein perturbations on craniofacial (beak) formation. The objectives are to 1) identify the roles of SOXE factors during neural crest (NC) specification and the epithelial-mesenchymal transition (EMT) in chick versus quail embryos, 2) determine the cadherin code that controls NC cell fate and EMT in chick vs quail, and 3) quantify the effects of SOXE and cadherin perturbations on craniofacial beak structure. Collectively, this work will shed light on the molecular, cellular, and organismal-level mechanisms that drive neural crest cell formation and will significantly increase our understanding of how organisms use the same factors to drive differential morphogenesis. 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.