Organogensis

VI.1 COORDINATORS
VI.2 PARTICIPANTS
VI.3 SUMMARY
VI.4 INTRODUCTION
VI.5 SPECIFIC AIMS
VI.6 BACKGROUND AND SIGNIFICANCE

• VI.6.i General Background to Organogenesis
• VI.6.ii Interplay of Physical and Genetic Mechanisms in Organogenesis
  • VI.6.ii.a Cell Adhesion
  • VI.6.ii.b Chemotaxis and Haptotaxis
  • VI.6.ii.c Epithelial and Mesenchymal Tissues
  • VI.6.ii.d Epithelia and Cell Polarity
  • VI.6.ii.e Mesenchyme and Extracellular Matrix
  • VI.6.ii.f Mesenchymal Condensation
  • VI.6.ii.g Cell Excitability
  • VI.6.ii.h Reaction-Diffusion Mechanisms
  • VI.6.ii.i Differentiation
  • VI.6.ii.j Summary of Basic Mechanisms of Pattern Formation and Morphogenesis
  • VI.6.ii.k Neuronal Guidance, Fasciculation and Defasciculation
• VI.6.iii Background to Specific Experimental Systems
  • VI.6.iii.a Gastrulation
  • VI.6.iii.b Limb Development
  • VI.6.iii.c Innervation
    • VI.6.iii.c.1 Skeleto-muscular innervation
    • VI.6.iii.c.2 Retinotectal innervation
  • VI.6.iii.d Cardiovascular Development
    • VI.6.iii.d.1 Early vertebrate heart development
    • VI.6.iii.d.2 Trabeculation

VI.7 THEORETICAL FRAMEWORK
VI.8 PRELIMINARY RESULTS
VI.9 RESEARCH DESIGN AND METHODS
VI.10 RELATIONSHIP TO CYTOSKELETON (PROJECT 2) AND BIOLOGICAL NETWORKS (PROJECT 1)
VI.11 TIMELINE

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VI.5 SPECIFIC AIMS:

VI.5.i Develop Multiscale Experimental and Computational Models for Organogenesis Applicable to a Range of Developmental Processes:

1. We will use experimentation and modeling to study the adhesion and growth-factor-regulated movement of cells during gastrulation in chicken and zebrafish.
2. We will use experimentation and modeling to study the cell-cell adhesive interactions and cell-growth factor interactions involved in the development of the vertebrate limb.
3. We will use experimentation and modeling to study the cell adhesive and cell-growth factor interactions involved in neuronal pathfinding and fasciculation in the vertebrate limb and visual system.
4. We will use experimentation and modeling to study the growth factor-regulated formation of myocardial trabeculae in the developing mouse heart.
5. We will explicitly link the Organogenesis models to those of the Cytoskeleton and Network Projects to integrate cellular and sub-cellular simulations into a multiscale model.

VI.6 BACKGROUND AND SIGNIFICANCE:

VI.6.i General Background to Organogenesis:

Organogenesis is the establishment of functionally coordinated arrangements of tissues during embryonic development. It consists of three main processes, morphogenesis, differentiation, and pattern formation, which we can separate conceptually, although they typically occur in coordination with one another in space and time.

Morphogenesis is the shaping and molding of living tissues in three-dimensional space. In addition to its role in development, morphogenesis is central to regeneration, wound healing, and various pathologies. During morphogenesis, tissue masses may disperse, form internal foci of cell condensation, lengthen or shorten, or acquire lumens. They can also form sheets which may invaginate or evaginate, or develop one or more internal boundaries which restrict or prohibit cell mixing. Such compartmentalized tissues can either physically separate, or remain attached and engulf, or be engulfed by, one another. These processes produce the various body plans and organ forms characteristic of multicellular organisms, as well as tumors, abnormal polyps, and fibrotic lesions.

Differentiation is the biochemical diversification of cell types according to well-ordered lines of descent, or lineages. Because differentiation is a dynamical process that involves networks of transcription factors controlling one another's expression and the expression of other target genes, we consider it primarily as part of the Networks section of this application (Project 1).

Pattern formation is the establishment of specific spatial arrangements of differentiated cell types.