Principles of intra- and inter-species cis-regulatory variation in the primate neural crest

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Cis-regulatory changes play a central role in normal phenotypic variation within a species as well as in morphological divergence, yet the regulatory principles underlying emergence and modulation of human traits remain poorly understood. As part of my PhD work, I have used epigenomic profiling to annotate and explore the molecular effects of enhancer mutations using in vitro-derived neural crest cells. First, by exploiting high-frequency polymorphisms in human cell lines, we explored how mutations can cooperatively affect binding of key neural crest transcription factors at specific human enhancers. We then extended this analysis across species, using human and chimpanzee cranial neural crest cells to systematically and quantitatively annotate divergence of craniofacial cis-regulatory landscapes genome-wide. We found that epigenomic divergence is often attributable to genetic variation within TF motifs at orthologous enhancers, with a novel motif being most predictive of activity biases. We further explored the properties of this cis-regulatory change, revealing the role of particular retroelements, uncovering broad clusters of species-biased enhancers near genes associated with human facial variation, and demonstrating that cis-regulatory divergence is linked to quantitative expression differences of crucial neural crest regulators. This work provides a wealth of candidates for future studies on human craniofacial development and evolution, and demonstrates the value of "cellular anthropology, " a strategy of using in-vitro-derived embryonic cell types to elucidate both fundamental and evolving mechanisms underlying morphological variation in higher primates.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2016
Issuance monographic
Language English


Associated with Prescott, Sara L
Associated with Stanford University, Department of Developmental Biology.
Primary advisor Wysocka, Joanna, Ph. D
Thesis advisor Wysocka, Joanna, Ph. D
Thesis advisor Helms, Jill
Thesis advisor Kingsley, David M. (David Mark)
Thesis advisor Talbot, William
Advisor Helms, Jill
Advisor Kingsley, David M. (David Mark)
Advisor Talbot, William


Genre Theses

Bibliographic information

Statement of responsibility Sara L. Prescott.
Note Submitted to the Department of Developmental Biology.
Thesis Thesis (Ph.D.)--Stanford University, 2016.
Location electronic resource

Access conditions

© 2016 by Sara Lorraine Prescott

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