The cell biology of tissue polarity and epithelial patterning
Complex patterns of cellular arrangements are found in nearly every multicellular life form and within every organ in our body. From the scales that cover the wing of a butterfly to the checkerboard pattern of ciliated cells that line our inner ear, the form and architecture of a tissue is what enables its specialized function.
How do cells assemble into complex and precisely coordinated patterns?
How cells are arranged into highly ordered patterns during organ formation is one of the most fundamental questions in developmental biology. To assemble into functional tissues cells must integrate spatial and directional cues, which dictate the position of specific cell types and the direction of cellular structures.
Cells and their specialized structures are oriented and aligned across a tissue by the planar cell polarity pathway (PCP). Striking examples of planar polarized patterns are the stereocilia within the inner ear or the body hairs covering the mammalian epidermis. We use the mouse epidermis as a model to understand how complex cellular arrangements, such as hair follicles, become precisely oriented and aligned across long distances. Specifically we aim to:
Determine how cells ‘sense’ direction and communicate directional information to their neighbors.
Elucidate how cells assemble polarized structures in response to directional signals.
How is tissue architecture maintained during growth, renewal, and repair?
Our second area of research centers on understanding how tissues maintain their precise organization despite rapid growth during development, constant self-renewal throughout adult life, and repair after injury. Polarized epithelial cells confront a particular challenge when they need to divide: cellular contents that are asymmetrically distributed face unequal inheritance during division without some mechanism to ensure their equal distribution. We’ve identified a novel mechanism used by proliferating skin cells to ensure planar polarity is maintained whenever cells divide. Our current work focuses on identifying new regulators of cell polarity during mitosis and understanding the consequences on cell proliferation when tissue polarity fails to be maintained.
Danelle Devenport's research focuses on how cells assemble into highly ordered structures to produce functional organs. Currently, she studies how directional signals instruct cells to organize cellular structures at specific positions and orientations across a tissue. This phenomenon, called planar polarity, can be found in nearly all epithelial tissues but is particularly striking in epidermal structures like scales, feathers, and hairs that are precisely and coordinately aligned over the entire surface of the vertebrate body. Using mammalian epidermis as a model system, she is dissecting the mechanisms of how cells 'sense' direction and coordinate cellular morphogenesis over long distances. In addition, she focuses on how highly regenerative tissues maintain their precise organization despite continuous proliferation and turnover.
Her honors and fellowships include the Searle Scholars Award, Vallee Foundation Young Investigator Award, American Cancer Society Research Scholar Award, NIH K99/R00 Pathway to Independence Award, Ruth L. Kirschstein National Research Service Award for postdoctoral research, The Wellcome Trust Fellowship and PhD Studentship, Overseas Research Student Award from Cambridge University, International Student Fellowship from the University of British Columbia and a Howard Hughes Undergraduate Research Fellowship.
Danelle received her Ph.D. from the University of Cambridge in 2004 and was a postdoctoral fellow at The Rockefeller University until 2011. She holds an M.Sc. from the University of British Columbia and a B.S. from Humboldt State University in California.
Honors & Awards
- Innovation Fund Award, Princeton University
- Innovation Award, Department of Molecular Biology, Princeton University
- Vallee Foundation Young Investigator, Bert L and N Kuggie Vallee Foundation
- Ph.D., University of Cambridge
- M.Sc., University of British Columbia
- B.S., Humboldt State University in California
- 1.Basta L, Hill-Oliva M, Paramore S, Sharan R, Goh A, Biswas A, Cortez M, Little K, Posfai E, Devenport D. New mouse models for high resolution and live imaging of planar cell polarity proteins in vivo. Development. 2021;148(18). PMCID: PMC8487645
- 1.Goglia A, Wilson M, Jena S, Silbert J, Basta L, Devenport D, Toettcher J. A Live-Cell Screen for Altered Erk Dynamics Reveals Principles of Proliferative Control. Cell Syst. 2020;10(3):240–253.e6. PMCID: PMC7540725
- 1.Cetera M, Leybova L, Joyce B, Devenport D. Counter-rotational cell flows drive morphological and cell fate asymmetries in mammalian hair follicles. Nat Cell Biol. 2018;20(5):541–552. PMCID: PMC6065250
- 1.Pujol F, Hodgson T, Martinez-Corral I, Prats A-C, Devenport D, Takeichi M, Genot E, Mäkinen T, Francis-West P, Garmy-Susini B, Tatin F. Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization During Lymphatic Valve Morphogenesis-Brief Report. Arterioscler Thromb Vasc Biol. 2017;37(9):1732–1735. PMID: 28705793
- 1.Duncan J, Stoller M, Francl A, Tissir F, Devenport D, Deans M. Celsr1 coordinates the planar polarity of vestibular hair cells during inner ear development. Dev Biol. 2017;423(2):126–137. PMCID: PMC5369242
- 1.Cetera M, Leybova L, Woo F, Deans M, Devenport D. Planar cell polarity-dependent and independent functions in the emergence of tissue-scale hair follicle patterns. Dev Biol. 2017;428(1):188–203. PMCID: PMC5549468
- 1.Aw W, Heck B, Joyce B, Devenport D. Transient Tissue-Scale Deformation Coordinates Alignment of Planar Cell Polarity Junctions in the Mammalian Skin. Curr Biol. 2016;26(16):2090–100. PMCID: PMC5005808