Department of Craniofacial Biology, University of Colorado Denver, Aurora, Colorado, USA.
PLoS One. 2009 Dec 16;4(12):e8066. doi: 10.1371/journal.pone.0008066.
Orofacial malformations resulting from genetic and/or environmental causes are frequent human birth defects yet their etiology is often unclear because of insufficient information concerning the molecular, cellular and morphogenetic processes responsible for normal facial development. We have, therefore, derived a comprehensive expression dataset for mouse orofacial development, interrogating three distinct regions - the mandibular, maxillary and frontonasal prominences. To capture the dynamic changes in the transcriptome during face formation, we sampled five time points between E10.5-E12.5, spanning the developmental period from establishment of the prominences to their fusion to form the mature facial platform. Seven independent biological replicates were used for each sample ensuring robustness and quality of the dataset. Here, we provide a general overview of the dataset, characterizing aspects of gene expression changes at both the spatial and temporal level. Considerable coordinate regulation occurs across the three prominences during this period of facial growth and morphogenesis, with a switch from expression of genes involved in cell proliferation to those associated with differentiation. An accompanying shift in the expression of polycomb and trithorax genes presumably maintains appropriate patterns of gene expression in precursor or differentiated cells, respectively. Superimposed on the many coordinated changes are prominence-specific differences in the expression of genes encoding transcription factors, extracellular matrix components, and signaling molecules. Thus, the elaboration of each prominence will be driven by particular combinations of transcription factors coupled with specific cell:cell and cell:matrix interactions. The dataset also reveals several prominence-specific genes not previously associated with orofacial development, a subset of which we externally validate. Several of these latter genes are components of bidirectional transcription units that likely share cis-acting sequences with well-characterized genes. Overall, our studies provide a valuable resource for probing orofacial development and a robust dataset for bioinformatic analysis of spatial and temporal gene expression changes during embryogenesis.
由于遗传和/或环境原因导致的口面畸形是常见的人类出生缺陷,但由于负责正常面部发育的分子、细胞和形态发生过程的信息不足,其病因通常不清楚。因此,我们已经为小鼠口面发育衍生了一个全面的表达数据集,检测了三个不同的区域——下颌、上颌和额鼻突。为了捕获面部形成过程中转录组的动态变化,我们在 E10.5-E12.5 之间采集了五个时间点的样本,跨越了从突起建立到融合形成成熟面部平台的发育阶段。每个样本使用七个独立的生物学重复,以确保数据集的稳健性和质量。在这里,我们提供了数据集的概述,从空间和时间水平上描述了基因表达变化的各个方面。在这个面部生长和形态发生的时期,三个突起之间发生了相当大的协调调节,基因表达从参与细胞增殖的基因转变为与分化相关的基因。伴随而来的多梳和三翼基因表达的转变,大概分别维持了前体细胞或分化细胞中适当的基因表达模式。在许多协调变化之上,是转录因子、细胞外基质成分和信号分子的表达在突起之间的特异性差异。因此,每个突起的细化将由与特定细胞:细胞和细胞:基质相互作用相结合的特定转录因子组合驱动。该数据集还揭示了几个以前与口面发育无关的、具有突起特异性的基因,我们对其中一部分进行了外部验证。这些后者基因中的一些是双向转录单元的组成部分,它们可能与特征明确的基因共享顺式作用序列。总的来说,我们的研究为探索口面发育提供了有价值的资源,并且为胚胎发生过程中时空基因表达变化的生物信息学分析提供了一个强大的数据集。
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