Featured Research

from universities, journals, and other organizations

How To Make A Lung

Date:
September 21, 2009
Source:
University of Pennsylvania School of Medicine
Summary:
A tissue-repair-and-regeneration pathway in the human body, including wound healing, is essential for the early lung to develop properly. Genetically engineered mice fail to develop lungs when two molecules in this pathway, Wnt2 and Wnt2b, are knocked out.

# Normal and separate expression of Nkx2.1 (green) in lung endoderm and p63 (red) in esophagus endoderm (arrow) (Panel U). Activation of Wnt/beta-catenin results in reprogramming of esophagus endoderm to Nkx2.1 positive lung endoderm (panel V, arrow).
Credit: Edward Morrisey, PhD, University of Pennsylvania School of Medicine; Developmental Cell

A tissue-repair-and-regeneration pathway in the human body, including wound healing, is essential for the early lung to develop properly. Genetically engineered mice fail to develop lungs when two molecules in this pathway, Wnt2 and Wnt2b, are knocked out. The findings are described this week in Developmental Cell.

Related Articles


“We wanted to know the answer to a seemingly simple question: What is required to generate the lung in mammals?” asked senior author Edward Morrisey, PhD, Associate Professor of Medicine and Cell and Developmental Biology at the University of Pennsylvania School of Medicine.

“Wnt molecules are important for lung growth and we think that some of the molecules in the Wnt pathway are needed to specify lung progenitor cells and if not enough cells are ‘told’ to make a lung, an animal develops a faulty, smaller organ or even no lung,” says Morrisey, who is also the Scientific Director of the Penn Institute for Regenerative Medicine.

Several molecular signals are important for proper lung development but not much is known about the early signals that turn on the genes needed to specify the lung at the right place and time in the embryo. Clinically, understanding how a lung develops is important in treating or preventing a host of lung and pulmonary diseases in children. “Premature babies in particular often develop respiratory problems which can lead to health issues not only during infancy but also later in life” says Morrisey.

He also points out that pulmonary and cardiac development is intricately connected: “One thing that is coming out of these studies is that the lung and heart form together which is an important point to remember as pathways affecting one organ system can affect the other.” In fact, one of the Wnt knockout mice the team developed also has profound cardiovascular defects, he notes.

In the developing embryo, the lung, pancreas, liver, thyroid, and stomach all come from the foregut region, which starts out looking like a long tube. “These organs bud from this undifferentiated tube and go on to develop into specific tissue types,” explains Morrisey. “The lung is one of the last to bud off the foregut during development.”

The team focused on the Wnt pathway to see where and when Wnt molecules were expressed along the foregut tube, even before the lung starts to become a recognizable organ. “The lung is a relative late arriver,” says Morrisey. “The liver, pancreas, and other organs begin developing days earlier.” They found that the Wnt proteins Wnt2 and Wnt2b are expressed in the cells surrounding the foregut, right where the lung will eventually form. When they are knocked out, the animals completely lacked lungs.

Morrisey surmised that Wnt2 and Wnt2b were required to specify the early progenitors for the lung in the foregut. “We found that the Nkx2.1 gene, which is expressed in both lung and thyroid progenitor cells in the foregut, were absent only in the region where the lung was supposed to form and not in the thyroid progenitor cells.”

They confirmed this fine tuning of lung development by knocking out an additional gene in the Wnt pathway called beta-catenin in the early foregut, and these mice also did not develop lungs, but all the other foregut-associated organs developed properly. “This says that these two Wnt molecules are essential for specifying the lung but not other foregut-derived organs” explains Morrisey.

The Morrisey lab also showed that activation of the Wnt pathway resulted in formation of lung progenitors in both the esophagus and stomach where they are normally excluded. “The ability of Wnt to program esophagus and stomach endoderm to a lung fate points to the critical role this pathway plays in lung development and suggests the possible use of Wnt in generating lung epithelium from non-lung sources.”

First author Ashley Goss is a graduate student in the Morrisey lab and co-author Terry P. Yamaguchi, National Cancer Institute, made one of the knockout mice. This work was funded by the National Heart, Lung, and Blood Institute, the American Heart Association and the National Cancer Institute.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of Pennsylvania School of Medicine. "How To Make A Lung." ScienceDaily. ScienceDaily, 21 September 2009. <www.sciencedaily.com/releases/2009/08/090817190648.htm>.
University of Pennsylvania School of Medicine. (2009, September 21). How To Make A Lung. ScienceDaily. Retrieved March 1, 2015 from www.sciencedaily.com/releases/2009/08/090817190648.htm
University of Pennsylvania School of Medicine. "How To Make A Lung." ScienceDaily. www.sciencedaily.com/releases/2009/08/090817190648.htm (accessed March 1, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, March 1, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rehab Robot Helps Restore Damaged Muscles and Nerves

Rehab Robot Helps Restore Damaged Muscles and Nerves

Reuters - Innovations Video Online (Mar. 1, 2015) A rehabilitation robot prototype to help restore deteriorated nerves and muscles using electromyography and computer games. Ben Gruber reports. Video provided by Reuters
Powered by NewsLook.com
Could a $34 Smartphone Device Improve HIV Diagnosis in Africa?

Could a $34 Smartphone Device Improve HIV Diagnosis in Africa?

Reuters - Innovations Video Online (Feb. 27, 2015) A dongle that plugs into a Smartphone mimics a lab-based blood test for HIV and syphilis and can detect the diseases in 15 minutes, say researchers. Tara Cleary reports. Video provided by Reuters
Powered by NewsLook.com
Doctor Says Head Transplants Possible Within Two Years

Doctor Says Head Transplants Possible Within Two Years

Buzz60 (Feb. 27, 2015) An Italian doctor is saying he could stick someone&apos;s head onto someone else&apos;s body. Patrick Jones (@Patrick_E_Jones) reports. Video provided by Buzz60
Powered by NewsLook.com
How Your Dentist Could Help Screen You For Diabetes

How Your Dentist Could Help Screen You For Diabetes

Newsy (Feb. 27, 2015) A new study from researchers at New York University suggests dentists could soon use blood samples taken from patients&apos; mouths to test for diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins