期刊论文详细信息
BMC Developmental Biology
Histone deacetylase-4 is required during early cranial neural crest development for generation of the zebrafish palatal skeleton
Charles B Kimmel3  John H Postlethwait3  Shigeyuki Wakitani4  Hiroyuki Kato1  Vishesh Khanna3  Ingo Braasch3  Yukio Nakamura2  April DeLaurier3 
[1] Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan;Department of Orthopaedic Surgery, Showa-Inan General Hospital, Akaho 3230, Komagane, 399-4117, Japan;Institute of Neuroscience, 1254 University of Oregon, Eugene, OR, 97403, USA;Department of Health and Sports Sciences, Mukogawa Women’s University, Nishinomiya, 663-8137, Japan
关键词: Zebrafish;    Skeleton;    Palate;    Neural crest;    hdac4;    Cartilage;   
Others  :  1086608
DOI  :  10.1186/1471-213X-12-16
 received in 2012-01-05, accepted in 2012-04-30,  发布年份 2012
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【 摘 要 】

Background

Histone deacetylase-4 (Hdac4) is a class II histone deacetylase that inhibits the activity of transcription factors. In humans, HDAC4 deficiency is associated with non-syndromic oral clefts and brachydactyly mental retardation syndrome (BDMR) with craniofacial abnormalities.

Results

We identify hdac4 in zebrafish and characterize its function in craniofacial morphogenesis. The gene is present as a single copy, and the deduced Hdac4 protein sequence shares all known functional domains with human HDAC4. The zebrafish hdac4 transcript is widely present in migratory cranial neural crest (CNC) cells of the embryo, including populations migrating around the eye, which previously have been shown to contribute to the formation of the palatal skeleton of the early larva. Embryos injected with hdac4 morpholinos (MO) have reduced or absent CNC populations that normally migrate medial to the eye. CNC-derived palatal precursor cells do not recover at the post-migratory stage, and subsequently we found that defects in the developing cartilaginous palatal skeleton correlate with reduction or absence of early CNC cells. Palatal skeletal defects prominently include a shortened, clefted, or missing ethmoid plate, and are associated with a shortening of the face of young larvae.

Conclusions

Our results demonstrate that Hdac4 is a regulator of CNC-derived palatal skeletal precursors during early embryogenesis. Cleft palate resulting from HDAC4 mutations in human patients may result from defects in a homologous CNC progenitor cell population.

【 授权许可】

   
2012 DeLaurier et al.; licensee BioMed Central Ltd.

【 预 览 】
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