Embryology of Muscle Precursor Patterning
Charles Ordahl, discussion leader

Jonathan Cooke, Nicole Le Douarin, Monty Westerfield
The specification of muscle precursor cells in vertebrates begins as gastrulating cells from the paraxial mesoderm. Several patterning steps ensue. First, paraxial mesenchyme condenses to form epithelial somites which contain precursor cells for a variety of cell types, including all of the skeletal muscle of the body. The patterning of myogenic precursor cells in the somite, therefore, represents an important first step in myogenesis. The major goals of research in this area are to understand the cellular movements and molecular changes in these precursor cells that govern their entry into the myogenic lineage. Dr. Ordahl has used surgical manipulation of avian embryos to show that hypaxial and epaxial muscle groups are respectively prepatterned in the lateral and medial halves of the somite. Dr. Westerfield, using both genetics and cell lineage tracing, has defined two populations of cells, muscle pioneers and adaxial cells, which are critical to the early patterning of muscle development in zebrafish. Dr. LeDouarin is a world renowned pioneer in modern embryology. Her recent work has elucidated how the role of the axial mesoderm (the notochord) acts to pattern the somite and has a differential effect on the epaxial and hypaxial muscle precursors. Dr. Cooke has studied muscle development both in amphibian and avian somites. His recent work shows that antisense disruption of the vertebrate homologue of the Drosophila snail gene disrupts the medial-lateral organization of that part of the somite (the dermomyotome) from which muscle precursors appear. Thus, this session will introduce the conferees to a variety of systems in which the early muscle pattern formation is studied and will provide a foundation for contiuity in later sessions.

Genetics of Muscle Precursor Patterning
Nadia Rosenthal, discussion leader

Susan Abmayr, Robb Krumlauf, Peter Rigby
Genetic analysis of development in flies and mammals has led to a new level of understanding about the role played by genes and gene products in the patterning of developing tissues. This session will focus on new discoveries regarding genetic control of muscle patterning. Using transgenic mice, Dr. Rosenthal has discovered novel genetic regulatory (cis-acting) elements that exert spatial (as opposed to tissue-specific) control of gene expression. Dr. Krumlauf, widely known for his work on the genetic control of the central nervous system, is also concerned with specification of somite identity by patterned expression of Hox genes. Dr. Rigby has used transgenic approaches for the analysis of patterned expression of muscle genes controlled by the myoD family of proteins. Thus, the work of Drs. Rosenthal, Krumlauf, and Rigby complement one another and provide a framework for understanding rostro-caudal patterning of vertebrate muscle systems. Dr. Abmayr, on the other hand, has done pioneering work on the genetics and molecular biology of early specification of muscle precursor cells in Drosophila, a system which provides a useful model for understanding vertebrate systems. In summary, this session will complement the earlier session by articulating diverse genetic views on early muscle patterning.

Tissue Induction of Myogenic Precursor Cell
Charles Emerson, discussion leader

John Gurdon, Andrew Lassar, Marc Tessier-Lavigne
The early patterning of myogenic precursors within the somite is governed by extrinsic signals arising from surrounding tissues in the embryo. The precise sources of these signals is now becoming known via combined efforts of molecular biology and experimental embryology. This session will highlight recent advances in the analysis of tissue induction of muscle precursor cells. Dr. Emerson is an internationally known leader in muscle molecular biology and has recently turned his attention to the role of developing neural tube induction of myogenic cells in the early somite. Dr. Tessier-Lavigne has used in vitro tissue recombination experiments to show that early patterning of muscle precursors in the early somite dermomyotome is under the control of the overlying skin ectoderm, a tissue previously unknown to play arole in muscle development. Dr. Gurdon is one of the world's premier scientists and molecular embryologists who has, for the past several years, turned his attention to muscle induction in amphibian embryos. He has elucidated the presence of both intrinsic determinants and community effects in the specification of early muscle cells in that system. Dr. Lassar, one of the co-discoverers of myoD, has recently showed that a series of combinatorial signals from varying regions of the neural tube are important in the early specification of myogenic precursors in the somite. This session, therefore, follows on the previous day's session by covering a wide variety of new experimental paradigms that seek to define the tissue interactions in the early embryo that lead to the specification of myogenic precursor cells.

Emergence and Diversication of Myogenic Precursor Lineages
Giulio Cossu, discussion leader

Mindy George-Weinstein, Stephen Hauschka, Cynthia Lance-Jones
Muscle precursors in the somite give rise to diverse muscle lineages depending upon both intrinsic and extrinsic forces. This session will concentrate on this lineage diversification and its genetic and epigenetic control. Dr. Cossu is internationally known for his in vitro analysis of myogenetic lineages in mouse somite. Dr. Lance-Jones, widely known for her work on early development of the peripheral nervous system, has recently elucidated the emergence of specific fiber lineages in the early developing limb. Dr. Hauschka was one of the first to discover developmental stage-dependent muscle lineages and their dependence on the extracellular milieu. His recent work using experimental embryology and molecular biology have made important inroads into the understanding of muscle lineage diversification. Dr. George-Weinstein has used in vitro culture to identify potential myogenic lineages within the pre-somitic mesoderm and the blastoderm of chick embryos. This session, therefore, will provide the broad basis for discussion of myogenetic lineages and their determination in the early developing vertebrate embryo.

Extracellular Matrix Signalling of Myogenic Precursors
Stephen Kaufman, discussion leader

Richard Hynes, Karen Knutsen, Anna Starzinski-Powitz
The extrinsic signals that govern myogenic specification act in concert with the extracellular matrix. This session will be one of the first at a muscle meeting to focus attention on the role of the extracellular matrix in the specification of muscle. Recent advances have shown that the extracellular matrix plays a determinative role in this specification process by interaction with specific cellular receptors. Drs. Kaufman and Hynes have worked extensively in the analysis of the integrin receptor, which interacts with a variety of extracellular matrix molecules. These speakers will address the molecular biology of these interactions as well as genetic analysis of the role of specific receptor subunits in patterning of early muscle precursor cells. Drs. Knutsen and Starzinski- Powitz will discuss their work on the role of cadherins and catenins in the specification of muscle precursors. This session should provide a broad foundation for discussions of the extensive role that extracellular matrix plays in the emergence of muscle precursor cells.

Cell-Cell Signalling in Myogenic Specfication
Rick Derynck, discussion leader

Lee Niswander, Brad Olwin, David Sassoon
The role of growth factors in muscle differentiation has been extensively studied over the past twenty years. Recent work, however, shows that growth factors also play pivotal roles in the early specification of myogenic precursor cells. This session will present recent work showing how such growth factor-precursor cell interactions occur and strategies for combining molecular biology and experimental embryology to study this process. Dr. Derynck is internationally recognized for his pioneering work on TGF and its receptors. He will present new information on the role of this and other growth factors in the specification of myogenic precursors in the somite. Dr. Olwin will present new information on the role of FGFs and FGFRs in the specification of and migration of muscle precursors in the developing limb bud and somite. Dr. Niswander has performed pioneering work on the role of growth factors and growth factor receptors in the developing limb bud. She was the first to show, for example, that FGF can replace the apical ectodermal ridge (AER) in the control of limb outgrowth. Dr. Sassoon will discuss his recent work on the role of wnt proteins in muscle development. Thus, this session will focus on the role of growth factors at earlier stages of muscle development than are conventionally presented at muscle meetings.

Molecular Control of Myogenic Determination
Bernardo Nadal-Ginard, discussion leader

Hans Arnold, Margaret Buckingham, Eric Olson, Harold Weintraub
The discovery of the myoD family of genes six years ago established the first molecular paradigm for vertebrate specification. In the intervening period a broad understanding of this class of transcriptional activation proteins has emerged. This session will focus on the molecular/genetic mechanisms that govern myogenic specification. Dr. Nadal-Ginard is internationally known for his work in muscle molecular biology. He will discuss his recent work on the coupling of myoD and the retinoblastoma gene product (RB) with the control of the cell cycle differentiating myogenic cells. Dr. Olson is widely known for his extensive contributions to the understanding of the molecular biology of myogenic determination genes. He will discuss his work on the genetic analysis of these genes in mammalian and non-mammalian systems. Dr. Arnold will discuss the embryonic effects resulting from targeted knockout of specific members of the myoD family. Dr. Weintraub, the co-discoverer of myoD, will present his recent work on the regulation of early muscle specification via interaction of novel gene products with the myoD family of proteins. Dr. Buckingham is an acknowledged world leader in the study of early patterning expression of myogenic determination genes in the paraxial mesoderm. This session will give broad overview of recent advances in the molecular mechanisms of myogenic specification and will provide a dynamic basis for the discussion of this key aspect of muscle development.

Keynote Address
Bodo Christ
It was over twenty years ago that Dr. Christ irreversibly altered the course of muscle research when he discovered that the somites are the source of all myogenic precursor cells in the body. During the intervening period, he has made enormous contributions to our understanding of the embryology of the somite in the general and myogenic precursor cells in particular. His recent work on the development of the myotome has established a physical model for myogenic precursor development that provides a crucial foundation for the molecular analysis of this process. He will present an overview of the extensive embryological information on muscle development and his recent experiments to define the precursor populations that emerge from the developing somite. This is a rare opportunity for an American audience to hear a full-length presentation by this individual of his extensive body of work and insights into myogenic specification during embryonic development.

Molecular Basis of Muscle Diseases
Kevin Campbell, discussion leader

Helen Blau, David Housman, Leslie Leinwand, Rick Steinhardt
Genetic diseases of muscle, in particular muscular dystrophy, continue to afflict a high percentage of individuals born in the western world. The mechanistic basis for these diseases continues to be poorly understood, despite advances in molecular and developmental biology of muscle. It is fitting, therefore, for this conference to close with a focus on current models for these muscle diseases because these may apply to our basic understanding of muscle embryology and vice versa. While far from being comprehensive, this session focuses on diverse views of the molecular mechanistic aspects of inherited muscle disease. Dr. Campbell is internationally known for his work on the molecular basis for muscular dystrophy. Dr. Steinhardt is a widely known for his work on muscle physiology and will present a new model paradigm for understanding the dystrohic phenotype that is based on calcium regulation. This model has not previously been presented at a major muscle meeting. Dr. Blau has made many seminal contributions to muscle molecular biology and the development and treatment models for inherited muscle diseases. Dr. Housman is an internationally acknowledged expert on inherited mitochondrial diseases in muscle. Dr. Leinwand has made seminal contributions to our understanding of the molecular control of muscle structural proteins. She will discuss important new information on the use of genetic manipulation to study and potentially treat diseases that affect muscle function.