The McCauley Lab is focused on the origin of vertebrate traits. We have several projects ongoing in the lab: The origin of glial cells in the vertebrate nervous system, the origins of epithelial to mesenchyme transition and migratory capability of neural crest cells, and development of genetic tools for control of invasive sea lamprey. We primarily use the sea lamprey, Petromyzon marinus, as a model but also take advantage of available models including zebrafish, and another basal vertebrate, the paddlefish, Polyodon spathula, to understand the evolution of developmental mechanisms in basal vertebrates.

Evolution of neural crest migration and epithelial to mesenchyme transition:

During vertebrate development, neural crest cells give rise to diverse tissues such as melanocytes, cartilage, bone, smooth muscle, neurons, and glia. Given their central importance, it is surprising that relatively little is known about their evolutionary origins. Recent research in the McCauley Lab has opened up a promising window into the origin of neural crest in basal, jawless vertebrates (lampreys). This work suggests that the developmental origin of neural crest cells and gene networks controlling their migration in lamprey are starkly different from the prevailing view of these processes in jawed vertebrates. We are currently investigating the molecular mechanisms that regulate the ability of neural crest cells to migrate, and also the locations where they arise in the developing lamprey embryo. We use a variety of embryo manipulation, imaging, and genetic tools to decipher the evolution of developmental mechanisms regulating neural crest, and have adapted modern genome editing tools, such as CRISPR/Cas to understand how genotype is related to phenotype in lampreys.

Evolution of gliogenesis and the origin of glial cells in vertebrates:

An interesting observation is that lampreys do not possess myelinating glial cells that are characteristic of all other vertebrates. This begs the question of what is the evolutionary origin of the cells that give rise to vertebrate myelin. These cells includes neural crest-derived Schwann cells of the peripheral nervous system, and oligodendrocytes in the central nervous system. Recent work in the lab suggests that lampreys possess cells that are similar to oligodendrocytes in their developmental origin and in expression of a suite of genes that define oligodendrocytes. Yet these oligodendrocyte-like cells in lamprey lack the myelinating capability of the oligodendrocytes that are present in other vertebrates. We are currently working to understand the evolutionary origins of myelinating glia by studying the development of similar glial cells that lack this ability. We use immunohistochemistry, genome editing, embryology, cell lineage tracing and imaging tools to investigate evolution and development of these traits. See Yuan et al. (2018) doi.org/10.1016/j.ydbio.2018.07.002. for additional information on this project.

Developing genetic tools for control of invasive sea lamprey

In addition to their interest as a model for understanding vertebrate evolution, sea lampreys are also a pest that invaded the Great Lakes early in the 20^th century, upsetting the ecology of the Great Lakes, and devastating the fishing industry. Genetic tools may offer a new strategy to control these invasive pests. We have begun a project to develop gene editing and genomic tools in sea lamprey. The purpose of this project, funded by the Great Lakes Fishery Commission, is to determine the feasibility of using gene editing and genomic tools to control invasive sea lamprey in the Laurentian Great Lakes bordering the United States and Canada. We will identify genes regulating various aspects of lamprey physiology (e.g., sex differentiation, spermatogenesis) and determine if they can be modified in a way that would reduce the number of invasive sea lamprey.  A synergistic effect of this project is that the molecular genetic tools we develop will have broad applications for understanding the basic biology of lampreys, toward a greater understanding of vertebrate evolution.  See York et al. 2020 (https://doi.org/10.1016/j.jglr.2020.03.010) for additional information.

Students entering the McCauley Lab are encouraged to develop their own research projects and are strongly encouraged to pursue independent funding opportunities.

• York, J.R., Zehnder, K., McCauley, D.W. The Evolution of Cellular EMT and migration. (2020). In The Origin and Evolution of Neural Crest Cells. Pp67-102. eds. B. Eames and I. Adameyko, series eds. B. Hall and S. Moody.
• York, J.R., Yuan, T. and McCauley, D.W. (2020). Evolutionary and developmental associations of neural crest and placodes in the vertebrate head: Insights from jawless vertebrates. Frontiers in Physiology,  doi.org/10.3389/fphys.2020.00986
• Yuan, T., York, J.R., and McCauley, D.W. (2020). Neural crest and placode roles in formation and patterning of cranial sensory ganglia in lamprey. Genesis (2020) May;58(5):e23356. doi: 10.1002/dvg.23356
• York, J.R., and McCauley, D.W. (2020). Functional genetic analysis in a jawless vertebrate, the sea lamprey: insights into the developmental evolution of early vertebrates. Journal of Experimental Biology 223, jeb206433. doi:10.1242/jeb.206433
• York, J.R., and McCauley, D.W. (2020). The origin and evolution of vertebrate neural crest cells. Open Biology 10: 190285. http://dx.doi.org/10.1098/rsob.190285
• York, J.R., Thresher, R.E., and McCauley, D.W. (2020). Applying functional genomics to the study of lamprey development and sea lamprey population control. Journal of Great Lakes Research https://doi.org/10.1016/j.jglr.2020.03.010
• York, J.R., Zehnder. K., Yuan, T., Lakiza, O., and McCauley, D.W. (2019). Evolution of Snail-mediated regulation of neural crest and placodes from an ancient role in bilaterian neurogenesis. Developmental Biology 453(2): 180-190.
• Yuan, T., York, J.R., and McCauley, D.W.  (2018). Gliogenesis in lampreys shares gene regulatory interactions with oligodendrocyte development in jawed vertebrates. Developmental Biology, 441(1): 176-190. doi.org/10.1016/j.ydbio.2018.07.002.
• York, J.R., Yuan, T., Lakiza, O., McCauley, D.W.  (2018). An ancestral role for Semaphorin3F-Neuropilin signalling in patterning neural crest within the new vertebrate head. Development, doi: 10.1242/dev.164780.
• York, J.R., Yuan, T., Zehnder, K., and McCauley, D.W. (2017). Lamprey neural crest migration is Snail-dependent and occurs without a differential shift in cadherin expression. Developmental Biology 428:176-187.