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The ultimate brow lift: HDAC8 in the epigenetic control of skull morhpgenesis

In the July 15th cover story of G&D, a research team led by Dr. Eric Olson at the UT Southwestern Medical Center at Dallas reports that the class I histone deacetylase 8 (HDAC8) enzyme regulates gene expression in the developing vertebrate skull.

HDAC8 overexpression is associated with a poor prognosis in human neuroblastoma patients. “As there are many different isoforms of histone deacetylases, it is crucial to understand the specific function of each — with the putative goal of targeting a specific subset for a specific disease process,” explains Dr. Mike Haberland, lead author on the study.

Dr. Olson’s team explored the role of HDAC8 in verterbrate skull morphogenesis, using a strain of knockout mice specifically lacking HDAC8 in cranial neural crest cells. Neural crest cells (NCCs) are a specialized group of embryonic cells that — among other things — have evolved to generate the
unsegmented vertebrate head, which has allowed vertebrates to transform from a passive, filter feeding animal into an active predator with paired eyes, an enlarged brain and protective skull, and ultimately, teeth and jaws.

The researchers found that HDAC8 deletion causes a deficiency of cranial NCCs, resulting in skull dysmorphism and instability, and perinatal death due to brain trauma. Microarray profiling revealed that HDAC8 represses multiple homeobox transcription factors that are active in the cranial NCC population, and function to pattern the frontal skull. Thus, HDAC8 has a crucial role in the epigenetic control of vertebrate skull development.


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