Regulation of Basement Membrane Composition and Dynamics During Organ Growth and Tissue Adhesion

Sherwood, David R

Keeley, Daniel Patrick

2020-02-10T17:27:54Z

2022-01-10T09:17:15Z

2019

Biology

Basement membranes are a specialized type of extracellular matrix found covering most tissues in animals. These structures are made up of many proteins, most notably laminin and type IV collagen, which form separate polymeric networks that are the core of the BM. BMs are involved in many cell and tissue scale processes during development and homeostasis, and misregulation of BM components lies at the heart of many pathologies. Despite their importance, many of the fundamental aspects of BM biology are not well understood. For example, the mechanisms that regulate differences in BM composition, dynamics, and ultrastructure remain largely unknown. One reason for this is the lack of a model to study these processes in vivo. This has also led to BM dependent processes, such as tissue adhesion through BMs, to be largely overlooked. In Chapter 1, I summarize some of my basic knowledge of BMs, highlight important areas that require further study, and review the process of tissue adhesion through BMs. In Chapter 2, I discuss the creation of an in vivo toolkit of endogenously fluorescently labeled BM components, show how these tools can be used to address questions surrounding BM composition and dynamics, and use these tools to identify papilin as a regulator of type IV collagen network architecture in growing tissues. In Chapter three, I explore the process of tissue adhesion through BMs in greater detail, and identify an enrichment of type IV collagen mediated by tissue specific modifications of the BM that is required to maintain stable BM adhesions between tissues. In Chapter 4, I discuss these findings in more detail, their implications, and future directions based off of this work.

https://hdl.handle.net/10161/20113

Biology

Developmental biology

Cellular biology

Basement membrane

CRISPR

Extracellular matrix

Live imaging

Tissue adhesion

Type IV collagen

Regulation of Basement Membrane Composition and Dynamics During Organ Growth and Tissue Adhesion

Dissertation

22.980821917808218