The Interactive Fly
Evolutionarily conserved developmental pathways
The importance of extracellular matrix (ECM) cannot be overstated. Disruptions of ECM can lead to uncontrolled cell growth, and the developmental destruction of ECM during amphibian molting leads to tissue death. Integration of components of the ECM with cell surface receptors and the consequent transduction of signals across the cell membrane serve to alter cell behavior and developmental fate. Even the intracellular signaling pathways associated with ECM components and their cognate receptors are conserved.
One conserved ECM component in Drosophila is Tenascin major. In Drosophila, loss of Tenascin major results in a pair rule phenotype, pointing to an early involvement of ECM in cell fate. Tenascin major is known to interact with integrins (see Myospheroid). Vertebrate tenascin is developmentally regulated and plays developmental roles in several vertebrate species. Some domains of tenasin are known to serve adhesive functions while others are counteradhesive in that they inhibit cell attachment to otherwise favorable substrates.
Another conserved ECM component, laminin, is a cruciform trimer, each subunit consisting of multiple domains. Laminins are known to interact with a variety of proteins including integrins and lectins. In tissue culture, Laminin is both a promoter and substratum for neurite outgrowth. In the fly, only one form of laminin has been characterized, but many proteins show homology to various domains of the laminin polypeptide. For example, Netrins, involved in axon guidance in many species, show extensive homology to common domains in each of the Laminin polypeptides. In vertebrates, laminin is not a single molecular complex, but a family of at least seven different complexes using alternative subunits. In the mouse, mutation in one laminin subunit results in a form of muscular dystrophy, while mutation in another leads to defects at the neuromuscular junction.
Nudel is an ECM component and is likely to serve as a scaffold for proteins involved in a protease cascade responsible for activation of the Epidermal growth factor receptor ligand known as Spätzle. nudel is one of over ten genes comprising the so-called dorsal group of genes that constitute a signaling pathway responsible for dorsal-ventral polarity. Immediately after fertilization, nudel and several other dorsal group genes and the gene cactus, generate a signal on the ventral side of the embryo. Nudel is a mosaic protein; it consists of a complex domain structure, including a serine protease, suggesting that it is involved in multiple protein interactions while carrying out its role in the protease cascade. Although Nudel is not a conserved protein, the serine proteases of vertebrates serve a vital function in degradation of ECM and consequent tissue remodeling. Another Drosophila extracellular serine protease is the protein Glutactin.
Collagen is a conserved ECM component with distinct developmental roles in Drosophila. Among collagen receptors are the integrins (see Myospheroid). Collagen IV in Drosophila is implicated in muscle attachment. Type IV collagen forms a network that provides the major structural support for basement membranes. Basement membranes are specialized forms of extracellular matrix with important functions in development. Decrease in type IV collagen in Drosophila results in defective muscle attachments. It is thought that type IV collagen acts to stabilize cell-matrix interactions (Borchiellini 1996).
The distributions of collagen IV and laminin were followed immunocytochemically during early wing development. In late third instar larvae, collagen IV and laminin surround the entire wing disc. For the first few hours following eversion of the disc, these ECM components line the basal surfaces of all epithelial cells in the wing pouch, both those destined to line the wing veins and those destined to become tightly apposed in the large intervein regions. Collagen IV and laminin persist in the ECM of these cells during the two initial rounds of apposition of dorsal and ventral wing surfaces; later they become restricted to the cells lining the veins. In an extreme allele of blistered, the wing balloons to form a single internal space. Collagen IV and laminin normally line all basal wing cell surfaces early in pupal development. Later, however, they still continue to line the entire cavity of the mutant wing rather than assuming a restricted distribution. In a wing completely devoid of veins, as found in rhomboid/veinlet/vein mutants, collagen IV and laminin are also present generally on basal surfaces at early times, but later are completely absent between the tightly apposed wing layers. The ECM distributions both in wild type wings and in mutants suggest that the matrix plays a role in the establishment of the wing venation pattern (Murray, 1995).
Borchiellini, C., Coulon, J. and Le Parco, Y. (1996). The function of type IV collagen during Drosophila muscle development. Mech Dev 58 (1-2): 179-191. PubMed Citation: 8887326
Murray, M. A., Fessler, L. I. and Palka, J. (1995). Changing distributions of extracellular matrix components during early wing morphogenesis in Drosophila. Dev. Biol. 168: 150-65. PubMed Citation: 7883070
date revised: 10 July 97
Developmental Pathways conserved in Evolution
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