Diaphragm Development and Congenital Hernias

Fluorescent microscope image of developing mouse diaphragm. Muscle in red, connective tissue and central tendon in green, nerves in blue.

The diaphragm is an essential mammalian skeletal muscle, as it is required for respiration and serves as a barrier between the thoracic and abdominal cavities. Unfortunately, it is also subject to developmental defects that lead to the common birth defect, congenital diaphragmatic hernias (CDH). CDH is common (1 in 3,000 births), and 50% of CDH babies die. Despite the diaphragm’s functional importance and the frequency and severity of CDH, the healthy development of the diaphragm, and what goes wrong during CDH has been poorly understood.

The Kardon lab used sophisticated mouse genetic studies to establish that the diaphragm arises from multiple embryonic tissues. One of these tissues, the pleuroperitoneal folds (PPFs), not only gives rise to the diaphragm’s muscle connective tissue and central tendon but also regulates the overall development of the diaphragm. Furthermore, they showed that genetic defects in the PPFs lead to CDH. Thus, these researchers showed that the PPFs are critical for normal diaphragm development and subject to genetic defects related to CDH. Their studies suggest future avenues for therapies to treat CDH.

Gabrielle Kardon, Ph.D. talking with Josh Hensley whose daughter had congenital diaphragmatic hernia (CDH).

References:

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Muscle connective tissue controls development of the diaphragm and is a source of congenital diaphragmatic hernias. Merrell AJ, Ellis BJ, Fox ZD, Lawson JA, Weiss JA, Kardon G. Nat Genet. 2015 May;47(5):496.

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