David H Hall

Publications (2)10.66 Total impact

• Article: The role of the laminin beta subunit in laminin heterotrimer assembly and basement membrane function and development in C. elegans.

  Gautam Kao, Cheng-chen Huang, Edward M Hedgecock, David H Hall, William G Wadsworth
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  ABSTRACT: Laminins are components of basement membranes that are required for morphogenesis, organizing cell adhesions and cell signaling. Studies have suggested that laminins function as alpha(x) beta(y) gamma(z) heterotrimers in vivo. In C. elegans, there is only one laminin beta gene, suggesting that it is required for all laminin functions. Our analysis is consistent with the role of the laminin beta as a subunit of laminin heterotrimers; the same cells express the laminin alpha, beta, and gamma subunits, the laminin beta subunit localizes to all basement membranes throughout development, and secretion of the beta subunit requires an alpha subunit. RNAi inhibition of the beta subunit gene or of the other subunit genes causes an embryonic lethality phenotype. Furthermore, a distinctive set of phenotypes is caused by both viable laminin alpha and beta partial loss-of-function mutations. These results show developmental roles for the laminin beta subunit, and they provide further genetic evidence for the importance of heterotrimer assembly in vivo.
  Developmental Biology 03/2006; 290(1):211-9. · 4.07 Impact Factor
• Article: Laminin alpha subunits and their role in C. elegans development.

  Cheng-Chen Huang, David H Hall, Edward M Hedgecock, Gautam Kao, Vassiliki Karantza, Bruce E Vogel, Harald Hutter, Andrew D Chisholm, Peter D Yurchenco, William G Wadsworth
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  ABSTRACT: Laminins are heterotrimeric (alpha/beta/gamma) glycoproteins that form a major polymer within basement membranes. Different alpha, beta and gamma subunits can assemble into various laminin isoforms that have different, but often overlapping, distributions and functions. In this study, we examine the contributions of the laminin alpha subunits to the development of C. elegans. There are two alpha, one beta and one gamma laminin subunit, suggesting two laminin isoforms that differ by their alpha subunit assemble in C. elegans. We find that near the end of gastrulation and before other basement membrane components are detected, the alpha subunits are secreted between primary tissue layers and become distributed in different patterns to the surfaces of cells. Mutations in either alpha subunit gene cause missing or disrupted extracellular matrix where the protein normally localizes. Cell-cell adhesions are abnormal: in some cases essential cell-cell adhesions are lacking, while in other cases, cells inappropriately adhere to and invade neighboring tissues. Using electron microscopy, we observe adhesion complexes at improper cell surfaces and disoriented cytoskeletal filaments. Cells throughout the animal show defective differentiation, proliferation or migration, suggesting a general disruption of cell-cell signaling. The results suggest a receptor-mediated process localizes each secreted laminin to exposed cell surfaces and that laminin is crucial for organizing extracellular matrix, receptor and intracellular proteins at those surfaces. We propose this supramolecular architecture regulates adhesions and signaling between adjacent tissues.
  Development 08/2003; 130(14):3343-58. · 6.60 Impact Factor