A Network of Transcription Factors Regulates Heart and Craniofacial Organ Development

An international team of researchers in the field of regenerative medicine have identified a set of transcription factors that functions as a hierarchical regulatory network, which initiates the formation of heart and craniofacial organs in the developing embryo.

They reported in the October 29, 2012, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that they had identified Lhx2 (LIM/homeobox protein) as a previously undescribed player during cardiac and pharyngeal muscle development.

Located in the pharyngeal mesoderm (PM), Lhx2 was found to interact genetically with two other cofactors, Tcf21 and Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Knockout of the genes encoding these transcription factors in mice resulted in animals with the specific cardiac features of this syndrome.

“Advances in regenerative medicine and developmental biology can now happen because we no longer require human embryos to generate stem cells,” said contributing author Dr. Chrissa Kioussi, associate professor of pharmacy at Oregon State University (Corvallis, USA). “The Nobel Prize this year was awarded to people who discovered how to make stem cells from adult biopsies.”

“In this work and in regenerative medicine, we care a great deal about all of these steps of cell differentiation,” said Dr. Kioussi. “If you know all the steps it takes to get from here to there, you can identify what went wrong and find ways to fix it. This is being done already with some disease problems, and this work will move us closer to being able to repair heart and craniofacial defects. Once we understand these genetic controls in sufficient detail, we can not only turn a skin cell into a stem cell, but also turn that stem cell into the type needed for the patient to recover. We may eventually be able to grow replacement organs from the patient’s cells.”

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Oregon State University