Jacek Topczewski, PhD Assistant Professor Pediatrics, CMRC Morphogenetic processes in vertebrate embryo Curricula: Developmental Biology Molecular Biology and Genetics E-mail:   j-topczewski@northwestern.edu

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Animal development required proper specification of different cell types and, at the same time, their organization in to multicellular arrangements such as tissue and organs. My laboratory investigates the mechanisms that control morphogenetic processes in vertebrate embryo. We are studying these processes in the zebrafish (Danio rerio) using a combination of genetic analysis with embryological and molecular methods. Transparency of zebrafish embryo together with a generation of fluorescent transgenic animals allows us to use of a high-resolution confocal microscopy for in vivo analysis of cell behaviors. Moreover, similarities in developmental programs among all vertebrates make zebrafish an excellent model for investigating human diseases and development.

We are focusing current efforts on the mechanism that shape zebrafish head skeleton. We are particularly interested in a role of non-canonical Wnt signaling in cartilage morphogenesis. Mutants with altered non-canonical Wnt signaling pathway exhibit similar cell behavior defects during gastrulation and cartilage morphogenesis. This observation led to hypothesis that non-canonical Wnt signaling controls cartilage elements morphology by modification of a chondrocytes behavior. My work on the characterization of the zebrafish knypek gene has revealed a new role for glypicans (heparan sulfate proteoglycan) in controlling morphogenetic movements during gastrulation by promoting non-canonical Wnt11 signaling. We are investigating function of non-canonical Wnt’s and their potential co-receptors glypicans in chondrocytes differentiation and polarization. As initial steps in craniofacial development are similar in all vertebrates those studies will help understand genetic basis for relatively frequent congenital anomalies causing abnormal development of the hard and soft tissue of the head and neck.

We are interested in developmental roles of other glypicans as those extracellular proteins can play an essential role by interaction with growth factors, chemokines, extracellular matrix proteins, enzymes and enzyme inhibitors. Glypicans can be involved in regulation of ligand-receptor interaction, and a control of ligand distribution, both within a tissue and on the cell surface. For example the clinical features of Simpson-Golabi-Behmel overgrowth syndrome, caused by mutation in the gene encoding Glypican 3 suggest that this protein is involved in regulation of cell survival and/or proliferation. One goal of my laboratory is to identify zebrafish glypicans and characterize developmental processes that they are regulating.

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