The Role of Laminin in Shaping the Cells that form the Midbrain-Hindbrain Boundary
Mentor 1
Jennifer Gutzman
Location
Union 240
Start Date
5-4-2019 12:40 PM
Description
Congenital brain defects can lead to physical or mental disabilities and are among the most common birth defects, occurring in 1 to 2 out of every 1000 live births. Determining how the brain acquires its shape during development is critical for elucidating the etiology of these defects. To understand formation of brain structure, we use the zebrafish model to study the mechanisms that regulate the first fold in the neuroepithelium; the highly conserved midbrain-hindbrain boundary (MHB). Laminin-111, a critical component of the basement membrane, is the primary laminin found along the developing neuroepithelium. It is a large protein composed of globular and rod-like domains arranged in a three-arm formation. Its unique structure makes it capable of anchoring epithelial cells to the extracellular matrix, as well as binding and signaling to other molecules within the basement membrane. Using live imaging, we found that the gamma chain of laminin-111 (lamc1), is required for proper MHB morphogenesis. However, the role for the other laminin chains, alpha1 (lama1) and beta1 (lamb1), in mediating cell shape changes remains unknown. Here, cell shape was analyzed in bashful (lama1) mutant embryos by live confocal imaging following membrane GFP-injection. We developed a new morphometric technique to analyze cells in 3D using digital sectioning, and uncovered a role for lama1 in mediating anisotropic cell shape to fold the neuroepithelium. Future experiments will investigate the role of the beta1 chain in mediating cell shapes required for MHB formation, and examine other basement membrane proteins such as agrin and collagen.
The Role of Laminin in Shaping the Cells that form the Midbrain-Hindbrain Boundary
Union 240
Congenital brain defects can lead to physical or mental disabilities and are among the most common birth defects, occurring in 1 to 2 out of every 1000 live births. Determining how the brain acquires its shape during development is critical for elucidating the etiology of these defects. To understand formation of brain structure, we use the zebrafish model to study the mechanisms that regulate the first fold in the neuroepithelium; the highly conserved midbrain-hindbrain boundary (MHB). Laminin-111, a critical component of the basement membrane, is the primary laminin found along the developing neuroepithelium. It is a large protein composed of globular and rod-like domains arranged in a three-arm formation. Its unique structure makes it capable of anchoring epithelial cells to the extracellular matrix, as well as binding and signaling to other molecules within the basement membrane. Using live imaging, we found that the gamma chain of laminin-111 (lamc1), is required for proper MHB morphogenesis. However, the role for the other laminin chains, alpha1 (lama1) and beta1 (lamb1), in mediating cell shape changes remains unknown. Here, cell shape was analyzed in bashful (lama1) mutant embryos by live confocal imaging following membrane GFP-injection. We developed a new morphometric technique to analyze cells in 3D using digital sectioning, and uncovered a role for lama1 in mediating anisotropic cell shape to fold the neuroepithelium. Future experiments will investigate the role of the beta1 chain in mediating cell shapes required for MHB formation, and examine other basement membrane proteins such as agrin and collagen.
