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The Molecular Regulation Of Diaphragm Development

3076 words - 13 pages


The diaphragm is a dome-shaped musculofibrous partition that separates the thoracic and abdominal cavities. The word “diaphragm” is Greek, and signifies a dividing wall or a closing or cutting off from (Mosby’s, 2008). This muscolofibrous structure is very important and if not the most important muscle in the body with regards to its main function, which is the involuntary action of breathing.

Embryological origins of the diaphragm

The diaphragm is a composite structure derived from several embryonic components. It forms during the 4th to the 10th week of embryonic life, and develops from four embryonic components, which are: septum transversum, pleuroperitoneal ...view middle of the document...

At the end of the 4th week of development, the septum transversum descends from the neck. By week 6, the pleuroperictoneal membranes extend medially and their free edges fuse with the mesentery of the esophagus and with the septum transversum, separating the pleural cavities from the peritoneal cavity, forming the primitive diaphragm (Restrepo et al, 2008). These components form the bulk of the diaphragm. The phrenic nerves arise from joined branches of cervical roots 3, 4, and 5 and supply the muscles fibers of the diaphragm. By week 8, as the diaphragm descends to the level of the lower thoracic vertebrae, it carries the phrenic nerves with it (2). The phrenic nerves then pass through the pleuropericardial membrane, and innervate the diaphragm, containng motor neurons for the diaphragm and sensory nerves for other abdominal structures (mediastinum, pleura, liver, gall bladder). (Mantilla and Sieck, 2008)

Figure 1. Embryologic origins of the diaphragm. The horizontal septum transversum (ST), pleuroperitoneal membranes (ppm), dorsal mesentery of the esophagus (dme), and body wall muscular fibers (Bw). Ao = aorta, Es = esophagus, IVC = inferior vena cava (Mantilla and Sieck, 2008).

Molecular development of the muscle of diaphragm

The diaphragm forms between weeks 4 and 10 of gestation in humans, and in the mouse between embryonic days 10.5 and 15.5 (gestation=18.5 days) (Ackerman and Greer, 2007). Past and current research on the molecular development of the diaphragm focuses on the genetic etiologies for the most common disorder of the diaphragm, which is congenital diaphragmatic hernia (CDH). The diaphragm has a characteristic appearance, which is similar in both human and mice (figure1.). As mentioned earlier, it is known that the diaphragm is derived from the mesodermal tissue. Muscularization of the diaphragm is more obvious along the perimeter of the diaphragm, while the central region is not. The muscle of the diaphragm proper is known to be derived from the paraxial mesoderm, while other tissues are derived from splanchnic or somatic mesoderm (Sweeney,1998). The somatic mesoderm is known to be the origin of the pleuroperitoneal folds, which form the posterior part of the diaphragm, while the septum transversum mesoderm gives rise to the anterior diaphragm. The muscles of the diaphragm, as well as the limb and tongue, are derived from the hypaxial muscle groups which are derived from the ventral myotome (Sweeney,1998). The population of the cells of ventral dermatome is identified as the expression of the gene Pax3 (Li et. Al 1999). These migrating muscle cells of the diaphragm also express Lbx1, however, loss of expression of this gene only has an effect on the muscles of the limb and tongue (brohmann , 2000). For the diaphragm to have correct muscularization, it requires complex coordination of precursor cells to delaminate, migrate, target diaphragmatic tissue, and differentiate (Ackerman and...

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