Kristen Kwan, Ph.D.

Cells must be organized into precise and stereotyped tissue and organ structures in order to function properly.  This process, known as morphogenesis, requires coordination and integration of signaling pathways, cell and tissue interactions, and cell fate decisions, often across hundreds or thousands of cells.  The eye, for example, must be assembled from numerous cells and tissues into a specific 3-dimensional form that can carry out basic visual functions.  When this process goes awry, structural aberrations in the eye can result in conditions in visual impairment.  Understanding the mechanistic basis of eye morphogenesis has implications for birth defects affecting eye structure, and will also inform efforts to build retinal tissues in vitro for transplantation therapies.

We know surprisingly little of the cellular and molecular mechanisms governing morphogenesis of most systems, largely due to our inability to observe organ formation as it happens in real time.  In order to understand eye morphogenesis, we use the zebrafish as our model system: external and rapid development, as well as optical transparency of the embryos, facilitates live imaging to directly visualize eye formation in the living embryo.

Therefore, we combine multidimensional live imaging, computational image analysis including custom-built software, and zebrafish molecular genetics to understand the basis of vertebrate eye formation.  Major focus areas of the lab include 1) signaling pathways (such as the conserved Hedgehog pathway) that drive cell movements; 2) extracellular matrix dynamics, especially controlling cell and tissue interactions; 3) disease modeling of human conditions of visual impairment affecting eye structure; and 4) method development for new image analysis and molecular tools.  Ultimately, our goal is to uncover the cellular and molecular mechanisms governing vertebrate eye formation under normal conditions, how it goes awry in disease, and how it has changed over evolutionary time.

Casey MA, Hill JT, Hoshijima K, Bryan CD, Gribble SL, Brown JT, Chien C-B, Yost HJ, and Kwan KM (2021). Shutdown corner, a large deletion mutant isolated from a haploid mutagenesis screen in zebrafish. G3 Genes|Genomes|Genetics; doi.org/10.1093/g3journal/jkab442

Lusk S and Kwan KM (2021).  Pax2a, but not pax2b, influences cell survival and periocular mesenchyme localization to facilitate zebrafish optic fissure closure. Dev Dyn, doi: 10.1002/dvdy.422 

Lusk S, Casey MA, and Kwan KM (2021).  4-dimensional imaging of zebrafish optic cup morphogenesis. J Vis Exp doi: 10.3791/62155

Bryan CD, Casey MA, Pfeiffer RL, Jones BW, and Kwan KM (2020).  Optic cup morphogenesis requires neural crest-mediated basement membrane assembly. Development, 147: dev181420 doi: 10.1242/dev.181420

Carney KR, Bryan CD, Gordon HB, and Kwan KM (2020).  LongAxis: a MATLAB-based program for 3D quantitative analysis of epithelial cell shape and orientation.  Dev Biol doi: 10.1016/j.ydbio.2019.09.016 

Gordon HB*, Lusk S*, Carney KR, Wirick EO, Murray BF, and Kwan KM (2018).  Hedgehog signaling regulates cell motility and optic fissure formation during vertebrate eye morphogenesis.  Development, doi:10.1242/dev.165068

Bryan CD, Chien CB, and Kwan KM (2016).  Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis.  Dev Biol, 416(2), 324-37.

Kwan KM, Otsuna H, Kidokoro H, Carney KR, Saijoh Y, Chien CB (2012). A complex choreography of cell movements shapes the vertebrate eye. Development, 139(2), 359-72.

Kwan KM, Fujimoto E, Grabher C, Mangum BD, Hardy ME, Campbell DS, Parant JM, Yost HJ, Kanki JP, Chien CB (2007). The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs. Dev Dyn, 236(11), 3088-99.

Lowe CJ, Terasaki M, Wu M, Freeman RM Jr, Runft L, Kwan K, Haigo S, Aronowicz J, Lander E, Gruber C, Smith M, Kirschner M, Gerhart J (2006). Dorsoventral patterning in hemichordates: insights into early chordate evolution. PLoS Biol, 4(9), e291.

Kwan KM, Kirschner MW (2005). A microtubule-binding Rho-GEF controls cell morphology during convergent extension of Xenopus laevis. Development, 132(20), 4599-610.

Kwan KM, Kirschner MW (2003). Xbra functions as a switch between cell migration and convergent extension in the Xenopus gastrula. Development, 130(9), 1961-72.