Cell-to-tissue architecture in the nervous system

Tissue-level organization of cells in animals is supported by the basement membrane (BM), a planar polymer of extracellular matrix proteins that underlies epithelia and surrounds organs and nervous tissue. Understanding tissue architecture and its underlying cellular and molecular determinants is essential for deciphering the mechanisms of normal nervous system morphogenesis and altered physiology in disease and aging. In our laboratory, we use the fruit fly Drosophila melanogaster to study the secretion and assembly of the BM. Taking advantage of the sophisticated genetic tools available in Drosophila, and in combination with advanced imaging, we are investigating the biogenesis of BM components, their assembly into normal and fibrotic polymers, and their roles in the morphogenesis of the nervous system, intercellular signaling, immune responses, regeneration and tumor progression.

A particularly interesting aspect of the biogenesis of the extracellular matrix is its trafficking through the secretory pathway. The huge dimensions of collagen and other matrix proteins make them prone to age-dependent aggregation and challenge our current models of how secretion works. In this regard, we are examining the highly specialized organization of the secretory pathway in neurons and their so-called “Golgi ouposts”: Golgi fragments lacking the polarized organization typical of this organelle. Understanding outpost formation may shed light on the causes and consequences of Golgi fragmentation, notably increased in neurodegenerative diseases.