Histone deacetylase-4 is required during early cranial neural crest development for generation of the zebrafish palatal skeleton.
Histone deacetylase-4 is required during early cranial neural crest development for generation of the zebrafish palatal skeleton.
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DOI：
10.1186/1471-213x-12-16
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发表时间：
2012-06-07
影响因子：
--
通讯作者：
Kimmel CB
中科院分区：
文献类型：
--
作者：
DeLaurier A;Nakamura Y;Braasch I;Khanna V;Kato H;Wakitani S;Postlethwait JH;Kimmel CB
组蛋白去乙酰化酶-4（Hdac 4）是抑制转录因子活性的II类组蛋白去乙酰化酶。在人类中，HDAC 4缺乏与非综合征性口裂和短指（趾）智力迟钝综合征（BDMR）伴颅面异常有关。我们在斑马鱼中鉴定了hdac 4，并描述了其在颅面形态发生中的功能。该基因以单拷贝形式存在，并且推导的Hdac 4蛋白质序列与人HDAC 4共享所有已知的功能结构域。斑马鱼hdac 4转录本广泛存在于胚胎的迁移性颅神经嵴（CNC）细胞中，包括眼睛周围迁移的人群，以前已被证明有助于早期幼虫腭骨骨架的形成。注射hdac 4吗啉代（MO）的胚胎具有减少或不存在的CNC群体，这些CNC群体通常迁移到眼睛内侧。CNC衍生的腭前体细胞在迁移后阶段不会恢复，随后我们发现发育中的软骨腭骨骼缺陷与早期CNC细胞的减少或缺失相关。腭骨缺损主要包括筛骨板缩短、裂开或缺失，并与幼仔面部缩短有关。我们的研究结果表明，Hdac 4是在早期胚胎发育过程中的CNC衍生的腭骨骨骼前体的调节剂。人类患者中HDAC 4突变导致的腭裂可能是由于同源CNC祖细胞群中的缺陷造成的。
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. 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. 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.