Hubbard Lab

During the development and maintenance of tissues and organs, cells must decide whether, when, where and how much to proliferate. Improper control of cell proliferation can lead to developmental defects and cancer. We are focusing on the relatively unexplored area of the control of pattern and extent of germline proliferation as a model for this process. In particular, we are interested in signaling between somatic cells and the germ line that influences germline proliferation during development. Our entry into this area is aided by our identification and analysis of C. elegans mutants that have germline tumors. We are using our detailed knowledge of germline tumor formation to design and carry out large-scale genetic screens - including RNAi-based screens - to identify genes that affect tumor formation. These approaches have identified candidate genes including genes involved in the insulin signaling pathway.

Developmental Genetics

The core question of developmental biology is how spatial organization of the body plan is achieved during embryogenesis such that a fertilized egg cell will give rise to a highly structured organism. Due to the identification and characterization of genes in several organisms and extensive progress in gene technology, many developmental processes are now being understood at the molecular level. One of the more important lessons from these studies is that homologous genes have related functions in invertebrates such as fruit flies and vertebrates such as the mouse. This insight implies that developmental processes will probably be best understood by integrating findings from several different organisms, each of which provides its own particular experimental advantages.

Scientists in the Developmental Genetics Program study a number of diverse developmental questions including: Establishment of the body axis by morphogen gradients, Regionalization of the embryonic xbrain into different structural and functional regions, Neural stem cell allocation and differentiation, Axon navigation and branching, Development of the embryonic eye, Heart development and analysis of heart function, Germ line development. Each research program integrates a genetic approach with the study of a variety of cellular processes like cell determination, cell lineage, and cell to cell signaling. A broad-organismal approach is provided through the use of a variety of experimental organisms, including Drosophila, chicken, mouse, rat and zebrafish.

Administrative Assistants:

Knaut Lab

Embryonic development involves extensive cell and tissue movements. Cells are often born far from their final position and face the challenge of navigating through the embryo to reach their destination and assemble into organs. To accomplish this task, they have to correctly interpret guidance cues, interact with various tissues along their migratory route and communicate with each other. We are trying to understand these principles using two different models: (1) The clustering of individual neuronal precursors into a ganglion and (2) the migration of muscle and cartilage precursors into the head.

Fishell Lab

The Fishell laboratory uses the mouse as a model system to study human brain development. The mammalian brain transits during late embryonic development from an undifferentiated neuroepithelium to the exquisitely organized structure seen at birth. Central to the emergence of this organization is the precise coordination of proliferation, patterning and cell migration.

Examination of the mouse telencephalon (front portion of the embryonic forebrain) over a four-day period illustrates the contribution of these three fundamental forces. During this time period distinct regions of the telencephalon are allocated and cell types within these regions are generated in appropriate numbers. To understand the cellular and molecular basis of these events, we use a wide range of methods, through which a picture of the logic by which telencephalic patterning is established is beginning to emerge. We now wish: 1) to understand the biochemical interactions by which specific signaling molecules initiate intrinsic programs that result in neuronal specification; 2) to better understand the transcription factor complexes that bestow unique cell character through their promotion of characteristic patterns of gene expression; 3) to explore the relationship between early signaling molecules and transcription factors and the mature neuronal phenotypes they give rise to.

Lehmann Lab

Early in the development of most organisms, primordial germ cells (PGCs) are set aside from those cells which form the organs and tissues of the body. Although capable of giving rise to a new organism, germ cells are highly specialized. In many species, germ cells form in a specialized cytoplasm that is synthesized during oogenesis and deposited in the egg. The location of this specialized cytoplasm, containing key determinants for early development, determines where germ cells will form. Upon formation, PGCs migrate on a distinct path through the developing embryo in order to reach a specific population of somatic cells where cellular interactions essential for the differentiation of the gonad take place.

We are interested in the following aspects of germ cell development: 1) How is polarity established in the oocyte such that germ plasm is only assembled at one egg pole? 2) What are the critical components of the germ plasm that make germ cells different from somatic cells? 3) What guides germ cells during their migration in the embryo? We study these questions in Drosophila, where critical molecules involved in any aspect of development can be efficiently identified using genetics.

Nance Lab

During the morphogenetic movements of gastrulation, cells that will form internal tissues become positioned within the interior of the developing embryo.   We use the nematode C. elegans as a model to understand some of the basic cellular events that occur during gastrulation.   C. elegans gastrulation involves the ingression of cells into a small blastocoel cavity in the interior of the embryo.   We are interested in understanding 1) how the blastocoel cavity forms, 2) how ingression movement occur, 3) how ingressions are triggered and patterned, and 4) how early embryonic cells acquire an apicobasal polarity that is important for blastocoel formation and ingression.   C. elegans is ideally suited for such studies, since individual cell movements can be followed in the optically clear embryo and genes involved in gastrulation can be identified using genetics.

Torres-Vazquez Lab

The vertebrate vasculature displays a highly reproducable and pervasive anatomy, required for carrying its multiple vital funtions. Consequently, defective vessel growth contributes to the patogeneis of multiple human diseases. To understand the genetic pathways and cellular strategies used by developing vessels to acquite their architecture, we are using genetic approaches and imaging tools to study vascular development in zebrafish.

Treisman Lab

We have three general areas of interest in the lab. The first is pattern formation in the Drosophila eye disc. We have used a genetic mosaic screen to identify novel genes required for the normal pattern of photoreceptor differentiation. Several of these genes have given us insight into the mechanism of Hedgehog signaling and the role of the cytoskeleton in differentiation. Secondly, we are interested in the interaction of signaling pathways with the general transcriptional machinery. We have evidence that subunits of the mediator complex and the Brahma chromatin remodeling complex are specialized to transmit certain signals. Finally, we are interested in axon guidance in the visual system, particularly in the mechanism by which the R7 photoreceptor finds its correct target layer.

Yelon Lab

Organogenesis requires the arrangement of multiple cell types into a specific pattern essential for the organ's proper function. This is especially true in the embryonic vertebrate heart, in which the intrinsic differences between its two major chambers, the anterior ventricle and the posterior atrium, are critical for unidirectional blood flow. There is evidence that ventricular and atrial lineages separate well before the bilateral regions of precardiac mesoderm fuse to form a midline heart tube. We are interested in identifying the molecules that control cardiac anterior-posterior patterning - the signals and receptors that provide early specification of ventricular and atrial lineages, as well as the downstream components of the chamber-specific differentiation pathways.

The zebrafish is an excellent subject, by virtue of the accessibility of its embryonic heart and the ease of classical genetic analyses. We have performed a genetic screen to identify mutations that disrupt cardiac chamber formation. These efforts yielded 20 mutations affecting ventricular development and one mutation affecting atrial development. Additional projects focus on other mutants with ventricular defects, as well as the sole mutant with an atrial defect. The future integration of these analyses should illuminate the genetic pathways responsible for cardiac chamber formation.