Molecular Biology Faculty
Lewis Thomas Lab, 247
Lab (609) 258-7534
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.
Shrestha R, Little KA,... Li W, Perlman DH, Devenport D. (2015) Mitotic Control of Planar Cell Polarity by Polo-like Kinase 1. Dev Cell. 33: 522-34. Pubmed
Devenport D. (2014) The cell biology of planar cell polarity. J Cell Biol. 207: 171-179. Pubmed
Devenport D, Oristian D, Heller E, Fuchs, E. (2011) Selective mitotic internalization of planar cell polarity proteins in proliferative epidermal stem cells. Nat Cell Biol. 13: 893-904. Pubmed
Devenport D, Fuchs E. (2008) Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol. 10: 1257-68. Pubmed
Tanentzapf G, Devenport D, Godt D, Brown NH. (2007) Integrin-dependent anchoring of a stem-cell niche. Nat Cell Biol. 9: 1413-18. Pubmed
Devenport D, Bunch TA, Bloor JW, Brower DL, Brown NH. (2007) Mutations in the αPS2 integrin subunit uncover new features of adhesion site assembly. Dev Biol. 308: 294-308. Pubmed
Devenport D, Brown NH. (2004) Morphogenesis in the absence of integrins: mutation of both Drosophila β subunits prevents midgut migration. Development. 131: 5405-15. Pubmed
Rogalski TM, Gilbert MM, Devenport D, Norman KR, Moerman DG. (2003) DIM-1, a novel immunoglobulin superfamily protein in Caenorhabditis elegans, is necessary for maintaining bodywall muscle integrity. Genetics 163: 905-15. Pubmed