Development of the diaphragm and genetic mouse models of diaphragmatic defects


  • Kate G. Ackerman,

    Corresponding author
    • Division of Genetics, Brigham and Women's Hospital, Harvard Medical School New Research Bldg 464, 77 Avenue Louis Pasteur, Boston, MA 02115.
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    • Kate G. Ackerman, M.D., is an Assistant Professor of Pediatrics at Harvard Medical School and a member of the Division of Genetics at Brigham and Women's Hospital and the Division of Emergency Medicine, Department of Medicine at Children's Hospital Boston. Dr. Ackerman is a pediatric intensivist with post-doctoral research training in mouse genetics. Dr. Ackerman's research focuses on understanding the pathophysiology of diaphragmatic defects and pulmonary hypoplasia in humans by investigating mechanisms of development in mouse models.

  • John J. Greer

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    • John J. Greer, Ph.D., is an Alberta Heritage for Medical Research Scientist and Professor of Physiology at the University of Alberta. Dr. Greer's research is in the area of perinatal neuromuscular control and development. A major component of his research focuses on the pathogenesis and etiology of congenital diaphragmatic hernia with a particular emphasis on understanding the defect to the diaphragm.

  • How to cite this article: Ackerman KG, Greer JJ. 2007. Development of the diaphragm and genetic mouse models of diaphragmatic defects. Am J Med Genet Part C Semin Med Genet 145C:109–116.


Improving our understanding of diaphragmatic development is essential to making progress in defining the pathogenesis and genetic etiologies of congenital diaphragmatic defects in humans. As mouse genetic technology has given us new tools to manipulate and observe development, a number of mouse models have recently emerged that provide valuable insight to this field. In this article, we review our current understanding of diaphragmatic embryogenesis including the origin of diaphragmatic tissue. We use rodent models to review the muscularization of the diaphragm and review selected genetic models of abnormal muscularization. We also review models of posterior diaphragmatic defects and discuss evidence for the pleuroperitoneal fold (PPF) tissue contributing to the diaphragm. Finally, we discuss models of anterior and central hernias. It may be simplistic to subdivide this review based on anatomic regions of the diaphragm, as evidence is emerging that defects in different regions of the diaphragm in humans and in mice may be etiologically related. However, at this time we do not have enough knowledge to make more mechanistic or genetic classifications though with time, genetic progress in the field of diaphragm development will allow us to do this. © 2007 Wiley-Liss, Inc.