Glowing worms provide live-action movies of the body's internal scaffolding

July 08, 2020

Duke University researchers have made the first time-lapse movies of the sheet-like latticework that surrounds and supports most animal tissues.

A thin layer of extracellular matrix known as the basement membrane lines many surfaces of the body such as the skin, blood vessels and urinary tract; and it surrounds muscles, fat, and peripheral nerves. While basement membranes play key roles in development, tissue function, and human disease, visualizing them in living organisms has been difficult to do, until now.

By genetically modifying C. elegans worms to create basement membrane proteins that glow under fluorescent light, the researchers say it's possible to see for the first time how basement membranes are assembled during development, and how they change and regenerate throughout life. The work may help to pinpoint what might be going wrong in human diseases ranging from kidney disease to invasive cancer.

"We wouldn't be here without basement membranes," said Duke biology professor David Sherwood, who led the research.

Basement membranes have been around for more than 600 million years, since the first multicellular animals evolved from their single-celled ancestors.

They're the Scotch tape that helps attach cells together to form tissues, maintaining healthy skin. They're the molecular sieves that filter blood in the kidneys, protect blood vessels and muscles from stretching and compression, and harbor growth factors that tell cells where to go, what to become, and when to divide.

But because most basement membranes lie deep within the body, beyond the reach of light microscopes, visualizing them in living tissues is hard to do in humans.

So Sherwood's team looked at them in millimeter-long transparent worms, using a gene-editing technique called CRISPR to label 29 basement membrane proteins with green glowing tags to see when and where each protein is found using time-lapse microscopy.

Getting a glimpse of these proteins in action inside a live animal offers a much more complete picture than previous experiments that looked at dissected and fixed tissues, which only provide a snapshot of proteins frozen in time, said postdoctoral fellow Eric Hastie.

"As a result, they have generally been thought of as 'boring' static structures," Hastie said

In some movies, the researchers tracked fluorescent proteins moving within the basement membrane lining the worm's throat. In others, they watched the rapid remodeling of the basement membrane surrounding the worm's gonad as it grew more than 90-fold in size.

Surprisingly, the movies show that most basement membrane proteins don't stay put after they're deposited. While some core components are static, the scientists were surprised to see that many proteins moved within this stable scaffolding.

"Our findings suggest basement membranes quickly change their properties to support mechanically active tissues and they may act as highways that allow growth factors to rapidly travel," Sherwood said.

"We've just started getting to play with this tool kit," Hastie said. But the team says their work offers a new way to study the basement membrane defects underlying tissue degeneration during aging, and diseases ranging from diabetes to muscular dystrophy.
-end-
This research was supported by the American Cancer Society (129351-PF-16-024-01-CSM) and the National Institutes of Health (F31 HD097901, F32GM103148, R35GM118049, R21HD084290).

CITATION: "Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement Within the Matrix Scaffolding," Daniel P. Keeley, Eric Hastie, Ranjay Jayadev, Laura C. Kelley, Qiuyi Chi, Sara G. Payne, Jonathan L. Jeger, Brenton D. Hoffman, and David R. Sherwood. Developmental Cell, June 24, 2020. DOI: 10.1016/j.devcel.2020.05.022

Duke University

Related Aging Articles from Brightsurf:

Aging-US: 'From Causes of Aging to Death from COVID-19' by Mikhail V. Blagosklonny
Aging-US recently published ''From Causes of Aging to Death from COVID-19'' by Blagosklonny et al. which reported that COVID-19 is not deadly early in life, but mortality increases exponentially with age - which is the strongest predictor of mortality.

Understanding the effect of aging on the genome
EPFL scientists have measured the molecular footprint that aging leaves on various mouse and human tissues.

Muscle aging: Stronger for longer
With life expectancy increasing, age-related diseases are also on the rise, including sarcopenia, the loss of muscle mass due to aging.

Aging memories may not be 'worse, 'just 'different'
A study from the Department of Psychological & Brain Sciences in Arts & Sciences adds nuance to the idea that an aging memory is a poor one and finds a potential correlation between the way people process the boundaries of events and episodic memory.

A new biomarker for the aging brain
Researchers at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have identified changes in the aging brain related to blood circulation.

Scientists invented an aging vaccine
A new way to prevent autoimmune diseases associated with aging like atherosclerosis, Alzheimer's disease, and Parkinson's disease was described in the article.

The first roadmap for ovarian aging
Infertility likely stems from age-related decline of the ovaries, but the molecular mechanisms that lead to this decline have been unclear.

Researchers discover new cause of cell aging
New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works.

Deep Aging Clocks: The emergence of AI-based biomarkers of aging and longevity
The advent of deep biomarkers of aging, longevity and mortality presents a range of non-obvious applications.

Intelligence can link to health and aging
For over 100 years, scientists have sought to understand what links a person's general intelligence, health and aging.

Read More: Aging News and Aging Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.