Top notch decisions in the developing airways bring insights into lung disease

Jun 08, 2009

In the normal lung, the airways are lined by a balanced mixture of ciliated, secretory and neuroendocrine cells which perform functions as diverse as air humidification, detoxification, and clearance of environmental particles. This balance can be altered dramatically by faulty adaptation responses of the lung to cigarette smoke or allergens in patients with Chronic Obstructive Pulmonary Disease (COPD) and asthma.

How these different cell types emerge from lung progenitor and how these fates are balanced in developing airways, remain an open question. A study from a research team led by Wellington Cardoso, MD, a professor at the Pulmonary Center Boston University School of Medicine and Director of the Program in Lung Development and Progenitor Cell Biology, sheds light into this problem.

The Notch pathway is a major regulator of cell fate decisions in developing cells from fruit flies to humans. Using mouse genetic models, the BU researchers inactivated Notch signaling in the and discovered that airways no longer formed secretory cells. Instead they became populated almost exclusively by ciliated cells. The researchers showed that this imbalance seems to result from the loss of a mechanism of cell fate choice triggered by the Notch called lateral inhibition.

"When you lose Notch signaling, you lose the ability to generate secretory cells that make the lining fluid critical for protection and integrity of airway, and the other fate, of ciliated cells is de-repressed" said Dr. Cardoso.

These findings help to understand how airways form and provide insights into how interfering with Notch signaling may be potentially useful as a therapeutic intervention in respiratory diseases, such as asthma and COPD, in which airways have an overabundance of secretory cells and paucity of ciliated cells in the airways. The link between hyperactive Notch and excessive secretion is now rapidly emerging from other recent reports.

Source: Boston University Medical Center

Explore further: Researchers uncover clues to flu's mechanisms

add to favorites email to friend print save as pdf

Related Stories

Asthma and smoker's lung: dry airways play a key role

Apr 07, 2008

Dry airways may not only play a central role in the development of the inherited lung disease cystic fibrosis, but also in much more common acquired chronic lung diseases such as asthma and smoker’s lung, the cigarette ...

Breast stem cell fate is regulated by 'notch'

Oct 08, 2008

A normal developmental protein that sometimes goes awry has been implicated in breast cancer. This discovery indicates the mechanism by which inappropriate expression of the Notch pathway may contribute to breast cancer.

Notch-ing glucose into place

Jan 27, 2008

A novel gene called rumi regulates Notch signaling by adding a glucose molecule to the part of the Notch protein that extends outside a cell, said researchers from Baylor College of Medicine in Houston and Stony Brook University ...

When is a stem cell not really a stem cell?

Aug 26, 2007

Working with embryonic mouse brains, a team of Johns Hopkins scientists seems to have discovered an almost-too-easy way to distinguish between “true” neural stem cells and similar, but less potent versions. Their finding, ...

Recommended for you

Small RNAs in blood may reveal heart injury

1 hour ago

(Medical Xpress)—Like clues to a crime, specific molecules in the body can hint at exposure to toxins, infectious agents or even trauma, and so help doctors determine whether and how to treat a patient. ...

Researchers uncover clues to flu's mechanisms

6 hours ago

A flu virus acts like a Trojan horse as it attacks and infects host cells. Scientists at Rice University and Baylor College of Medicine have acquired a clearer view of the well-hidden mechanism involved.

User comments : 0