Hazel Sive, PhD

Member, Whitehead Institute Professor of Biology, MIT 617.258.8242 phone 617.258.5578 fax sive@wi.mit.edu

Soon after fertilization, a developing embryo must decide what parts of its cell mass will form the anterior and posterior regions of its body, and how vital organs will form along this head-to-tail axis. Whitehead Member Hazel Sive uses frog and zebrafish to investigate how an embryo makes these early patterning decisions, and in particular, creates the pattern for neural development and brain formation [ sive research 220 kbps QuickTime]. Understanding this process may yield new insights into birth defects, neurological disease, and spinal cord injuries [ developmental biology 220 kbps QuickTime].

The Sive lab has developed a series of tests to define the genetic networks that control embryonic patterning. Early stages of embryonic development are virtually identical among frogs, fish, and humans, and many genes that control this process are conserved across species. By studying gene activity in frog and fish embryos, Sive and her colleagues have showed that neural patterning decisions are made much earlier than previously thought, at a time equivalent to a two and one-half week old human embryo. In fact, many of these decisions are made long before visible changes can be detected in the outward appearance of the cell.

Sive and her colleagues have identified more than 50 genes that participate in the embryo’s earliest decision to begin making neural tissue. One of the areas of the brain studied by the Sive lab is the hindbrain. The hindbrain forms crucial parts of the brain, including the cerebellum and medulla, as well as all the nerves that extend from the brain to the head.

The studies have identified genes that are essential to subdivide the hindbrain into its component parts. These insights may help researchers better understand birth defects caused by the brain malformations.

Recently, Sive and her colleagues also devised a novel genetic screen that enables researchers to isolate and identify mutations that affect brain development in the zebrafish. One of these mutations impedes an embryo’s formation of brain ventricles, cavities that lie deep within the brain and that form a circulatory system essential for normal brain function. Abnormal brain ventricular structure is seen in most forms of autism and schizophrenia. An extension of this initial study has led to definition of more than twenty mutants with brain ventricle defects. Analysis of the detailed defects and genes associated with the mutants is underway.

Sive is a Member of the Whitehead Institute and professor of biology at MIT. She arrived at Whitehead in 1991. In 1992, she was named a Searle Scholar and received a National Science Foundation Young Investigator Award. Sive earned her PhD from Rockefeller University in 1986.

Selected Publications

Lowery, L.A. and Sive, H. (2004). Strategies of vertebrate neurulation and a re-evaluation of teleost neural tube formation. Mech. Dev. Vol 121/10 pp 1189-1197.

Wiellette, E.L. and Sive, H. (2003). vhnf1 and FGF signals synergize to specify rhombomere identity in the zebrafish hindbrain. Development, 130:3821-3829.

Tropepe, V. and Sive, H. (2003). Can zebrafish be used as a model to study the neurodevelopmental causes of autism? Genes, Brain and Behavior 2, 268-281.

Wardle, F. and Sive, H. (2003). What's your position: The Xenopus cement gland as a paradigm of regional specification. BioEssays, 25:717-726.

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