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Thomas Schilling, Ph.D.
Professor
4462 Nat Sci II
University of California Irvine
Irvine, CA 92697
Lab Tel: (949) 824-7203
Office Tel: (949) 824-2479
Email: tschilli@uci.edu
Website: Lab Homepage
Zebrafish developmental genetics - Our laboratory uses genetics and molecular biology to study pattern formation in the early zebrafish embryo. The rapid development and simple anatomy of this teleost embryo, together with recently developed techniques for reverse genetics and a nearly complete genome sequence, make zebrafish a powerful molecular genetic system for studying the mechanisms of development. We focus on two areas: (i) neural crest specification and formation of the skeleton in the early embryo and (ii) long-range signals, morphogens, that pattern the anterior-posterior (A-P) axis of the nervous system. In both cases, we are interested in how gene functions translate into cell behaviours and the formation of tissues and organs.
A major focus of the work in our laboratory is to define as fully as possible the genetic and molecular pathways that establish the neural crest and its derivatives. Neural crest is a population of highly migratory cells that arise from the crests of the forming neural tube as it folds, and give rise to all of the body’s pigmentation, most of its peripheral nervous system, as well as the head skeleton. We have been analyzing and cloning the genes underlying a large library of mutations identified by their defects in the craniofacial skeleton. We have also identified downstream targets that we now believe control neural crest migration, and these share many similarities with other migrating cell types, such as metastatic cancer cells. A second, more recent focus of our lab is to understand the genetic and molecular pathways that specify the identities of cells along the A-P axis in the early embryo, including neural crest. Here we have begun to take a more computational, systems approach. The vitamin A derivative, retinoic acid (RA), is thought to be a diffusible factor that promotes posterior development. Zebrafish mutants in an enzyme that synthesizes RA, called Retinaldehyde dehydrogenase (Raldh2), have defects in the formation of segments in the hindbrain, known as rhombomeres, that each contain unique sets of interneurons and motor neurons. More recently, my lab has studied requirements for: 1) other Raldh enzymes, 2) RA receptors (RARs), 3) cellular RA binding proteins (CRABPs), and 4) RA degrading enzymes (Cyp26s), in signaling.