Wenbiao Chen
Ph.D., OSHU, 1997
Assistant Scientist, Vollum Institute
Joint Assistant Professor, Cell and Developmental Biology
Two of the fundamental questions in neurobiology are how different neuronal types arise during development and what prevents premature neuronal death during an organism's lifespan. Defects in each process are associated with many neurological disorders such as congenital blindness and late-onset neurodegenerative diseases. The Chen laboratory focuseson identifying the underlying mechanisms responsible for these neuronal processes using zebrafish as a model system. The small size and superb fecundity of zebrafish make it an idealvertebrate model for large-scale genetic analyses that in the past have traditionally been limited to invertebrates. We use retroviral insertions to generate mutations, making the identification of the mutated genes very easily.
The lab uses the retina as a model to study neuronal specification. The retina consists of onlyseven major cell types, all of which can be easily identified by their morphology and location. Currently, the lab is focusing on several previously identified insertional mutants that display retinal defects. Of the mutants being characterized, some affect retinal ganglion cells preferentially, while others affect photoreceptor cells. These mutants all affect novel genes. Chen and associates are using a variety of methods to define the genetic networks in which the proteins encoded by these genes function to regulate retinal cell differentiation and survival. Understanding the mechanisms underlying each phenotype will provide new insight into retinal development.
The Chen lab is also developing zebrafish models of human neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Huntington's disease, and Parkinson's disease. Although mutations in a number of genes have been implicated in these diseases, the exact nature of the molecular mechanisms responsible for these diseases is still unknown. We are planning to introduce similar mutations into the zebrafish genome to recapitulate these human pathologies. These transgenic models will then be used to search for genes that when mutated, enhance or suppress the progression of the diseases in zebrafish.
Golling G, Amsterdam A, Sun Z, Antonelli M, Maldonado E, Chen W, Burgess S, Haldi M, Artzt K,Farrington S, Lin SY, Nissen RM, Hopkins N. Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Nat Genet. 2002 Jun;31(2):135-40.
Burgess S, Reim G, Chen W, Hopkins N, Brand M. The zebrafish spiel-ohne-grenzen (spg) gene encodes the POU domain protein Pou2 related to mammalian Oct4 and is essential for formation of the midbrain and hindbrain, and for pre-gastrula morphogenesis. Development. 2002 Feb;129(4):905-16.
Chen W, Burgess S, Golling G, Amsterdam A, Hopkins N.High-throughput selection of retrovirus producer cell lines leads to markedly improved efficiency of germ line-transmissible insertions in zebra fish.J Virol. 2002 Mar;76(5):2192-8.Mar;76(5):2192-8.
Chen W, Burgess S, Hopkins N. Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Development. 2001 Jun;128(12):2385-96.
Amsterdam A, Burgess S, Golling G, Chen W, Sun Z, Townsend K, Farrington S, Haldi M, Hopkins N. A large-scale insertional mutagenesis screen in zebrafish.Genes Dev. 1999 Oct 15;13(20):2713-24