The laboratory studies the genetic basis by which form and structure are regulated during vertebrate development. We combine classical methods of experimental embryology with modern molecular and genetic techniques for regulating gene expression during embryogenesis. One of the classic systems for the study of embryonic development is the chick embryo, where grafting experiments have given profound insight into such questions as the patterning of developing limb axes, and the control of organogenesis. These classical experiments provide a context for interpreting modern molecular studies and the methods they employed also give us an additional set of tools for manipulating the embryo.

We are interested in the function and regulation of neural stem cells in the adult brain. We address questions about the mechanisms of neuronal birth, migration, and differentiation, and about how new nerve cells are integrated into and contribute to the function of postnatal brain circuits. The subventricular zone (SVZ), a very extensive germinal layer in the adult mammalian brain, contains large numbers of neural stem cells that can generate new neurons and glial cells throughout life. By means of chain migration, a novel form of neuronal translocation identified in our laboratory, young neurons born in the SVZ reach the olfactory bulb, where they become fully integrated into functional circuits. We have identified the neural stem cells in the SVZ.

The research interest of the lab is early embryogenesis in the nematode Caenorhabditis elegans. Our major focus for the past several years has been the analysis of a set of genes (the par genes) that are required for proper cytoplasmic partitioning in early embryos. Mutations in any of these six par genes lead to a maternal effect on the pattern and timing of the early cleavages (see movies). These loci define components of a maternally derived system for localization of cytoplasmic constituents during early cleavages. Failure to localize these constituents results in improper pattern and timing of cleavages, and leads to the ultimate death of the embryos. The protein products of four of the par genes are distributed asymmetrically at the periphery of early blastomeres.

The process by which embryos acquire their final shape involves the coordination of cell fate decisions with cell movement. We are taking an integrated approach to understanding this process in chordate embryos. We combine molecular manipulations, time-lapse imaging, and old-fashioned cut & paste embryology to investigate molecular signaling, individual cell behavior, and tissue rearrangement. By considering all of these components and how they affect the final body plan, we hope to build a comprehensive picture of early embryonic morphogenesis.

Craig Mello uses the nematode worm C. elegans as a model organism to investigate how embryonic cells differentiate and communicate during development. In addition, he is investigating the mechanism of RNA interference, a form of sequence-specific gene silencing triggered by double-stranded RNA. Dr. Mello is a 2006 Nobel Laureate.

Much of our work has been on mechanisms of brain wiring and other basic problems in the developmental biology of tissue growth. Over the past several years, we have started to apply insights from these fields to the problem of brain rewiring and regeneration and, more recently, to neuronal degeneration in both embryonic development and in neurodegenerative disease.

Our laboratory is interested in understanding how skeletal muscles form and grow in higher vertebrates. Most of our studies are carried out in the chick embryo. The aim of our studies is to understand how mesodermal cells, that have initiated their myogenic differentiation, will organize in time and space to form a functional muscle.

Dr. Salama is part of the research staff in Dr. David Haussler's lab at the Center for Biomolecular Science and Engineering at UC Santa Cruz. She is a member of the "Wet Lab" staff working on "Translational research—exploratory wet-lab validation of computational predictions". The Lab's research develops new statistical and algorithmic methods to explore the molecular evolution of the human genome, integrating cross-species comparative and high- throughput genomics data to study gene structure, function, and regulation. He focuses on computational analysis and classification of DNA, RNA, and protein sequences. Dr. Haussler leads the Genome Bioinformatics Group, which participates in the public consortium efforts to produce, assemble, and annotate the first mammalian genomes. His group designed and built the program that assembled the first working draft of the human genome sequence from information produced by sequencing centers worldwide and participated in the informatics associated with the finishing effort.

We are studying the cellular and molecular events induced by Sry expression to give us information about genetic switch genes, testis formation, and organ development in general. We have identified several pathways downstream of Sry, including cell migration, cell differentiation, proliferation, and many of the genes associated with these events. Experimental approaches include organ culture, transgenic mice, differential screens, confocal microscopy, biochemical and molecular techniques, classic mouse genetics, and comparative embryology.

The goal of our research is to learn the cellular, molecular and biomechanical mechanisms underlying morphogenetic movements during embryogenesis. One of the fundamental problems in developmental biology is determining what local cellular activities underlie the morphogenesis of cell populations. Analysis of this problem requires an integrated, multilevel approach. We examine the cell motility or shape changes that constitute the "motor" of morphogenetic movement with time lapse recording of low light videomicroscopy, or with confocal microscopy of labeled cells both in the whole embryo and explants.

The focus of our research with Xenopus and zebrafish embryos is the development of the primary germ layers that establish the major embryonic cell lineages, and the formation of the Spemann organizer, a specialized group of cells that organizes the body plan. We are using biochemical, molecular, genomic and embryological approaches to address two fundamental questions: 1) What are the transcriptional regulatory pathways that establish and refine pattern in the gastrula; and 2) How is an individual inductive signal used to generate distinct cellular responses during development?

We are interested in the regulatory mechanisms underlying vertebrate pattern formation, in both developmental and evolutionary contexts. For the past years, we have focused on Hox genes, a family of transcription factors that display special paradigmatic values, regarding their regulatory strategies, their functional organization and their key roles in morphological evolution.

We are interested in understanding the mechanisms that normally generate complex structures in the developing mammalian embryo. In particular, we have adopted the mammalian kidney, neural tube and limb skeleton as complex systems for analysis. In these models we have identified a number of critical signals, including members of the Wnt and Hedgehog pathways, that regulate the normal development of these structures. Our expectation is that a firm understanding of the normal regulatory principles that build organ systems will enable an informed and logical approach towards the long-term goal of regenerative medicine; an approach with enormous potential for the treatment of human disease.

Jaenisch, a Whitehead Founding Member, focuses on understanding epigenetic regulation of gene expression (the biological mechanisms that affect how genetic information is converted into cell structures but that don’t alter the genes in the process). Most recently, this work has led to major advances in our understanding of embryonic stem cells and “induced pluripotent stem” (IPS) cells, which appear identical to embryonic stem cells but can be created from adult cells without using an egg.

Dr. Battey's laboratory focuses on the molecular genetic analysis of biologic responses mediated by mammalian bombesin-like peptides and their receptors.

The research at the Institute of Cell Biology is aimed at understanding basic processes such as the control over cell differentiation, cell proliferation, cell fate maintenance and reprogramming as well as cell migration. The cells we are using to investigate these processes are primordial germ cells of the zebrafish (Raz) and mouse adult neuronal stem cells (Schwamborn).

The objective of our work is to understand early vertebrate development at the molecular level. We study this problem in both the amphibian Xenopus, and in the mouse. Xenopus embryos are large and easily manipulated, so that the function of various macromolecules, such as RNA and protein, can be assayed by microinjection into living embryos. Functional assays in Xenopus can then be complemented by genetic knockouts in the mouse, to gain fuller understanding of the normal requirements for gene action in the developing embryo.

Our research focuses on the development of the avian trunk neural crest. We are particularly interested in the mechanisms that segregate the neural crest lineage from the neural epithelium, the mechanisms that guide specific neural crest lineages along different migratory pathways, and the control of neural crest cell differentiation. The laboratory uses a number of experimental approaches to address cellular and molecular aspects of neural crest development including: surgical manipulation, cell culture, in vitro embryo culture, in ovo electroporation of expression plasmids, and gene knockdown using antisense oligonucleotides and morpholinos.

During embryogenesis the balance between cell death and proliferation must be constantly regulated in order for normal development to occur. To more fully understand the molecular control of this balance, my group focuses on how seemingly homogeneous populations of cells develop into three-dimensional tissues. The lab focuses specifically on the role of growth factors during the development and regeneration of the mammalian skeleton and brain using standard and conditional knock-out techniques.

Dr. Janet Rossant is a world-leading developmental biologist who has made major contributions to our understanding of how an embryo develops, how genes control development and how embryonic and other stem cells arise. Her research interests centre on understanding the genetic control of normal and abnormal development in the early mouse embryo, work that has shed light on how congenital anomalies in the heart, blood vessels and placenta arise.

We are interested in the function and regulation of neural stem cells in the adult brain. We address questions about the mechanisms of neuronal birth, migration, and differentiation, and about how new nerve cells are integrated into and contribute to the function of postnatal brain circuits. The subventricular zone (SVZ), a very extensive germinal layer in the adult mammalian brain, contains large numbers of neural stem cells that can generate new neurons and glial cells throughout life. By means of chain migration, a novel form of neuronal translocation identified in our laboratory, young neurons born in the SVZ reach the olfactory bulb, where they become fully integrated into functional circuits. We have identified the neural stem cells in the SVZ.

Dr. Kaufman's research interests focus on hematopoietic and endothelial cell development from human and non-human primate embryonic stem (ES) cells. This research uses ES cells to understand the earliest stages of hematopoiesis. In vitro and in vivo models are used to elucidate both extracellular protein interactions and intracellular genetic regulation that impact these developmental pathways. ES cells offer a unique model to investigate basic developmental biology and may serve as a therapeutic cell source to replace or repair cells or tissues damaged by disease or other degenerative processes.

Dr. Hans Keirstead is Associate Professor of Anatomy and Neurobiology and Co-Director of the Sue and Bill Gross Stem Cell Research Center at the UC Irvine Reeve-Irvine Research Center. In 2004, Hans Keirstead led his team of reserachers at UC Irvine to successfully develop a human embryonic stem cell derived treatment for acute spinal cord injuries in rats. That treatment was recently approved by FDA for clincial trials in humans with actue spinal cord injuries. The trial, which will be carried out by Geron Corporation, marks the first human embryonic stem cell trial ever approved in the U.S.