Research Article: Spatial and Temporal Analysis of Gene Expression during Growth and Fusion of the Mouse Facial Prominences

Date Published: December 16, 2009

Publisher: Public Library of Science

Author(s): Weiguo Feng, Sonia M. Leach, Hannah Tipney, Tzulip Phang, Mark Geraci, Richard A. Spritz, Lawrence E. Hunter, Trevor Williams, Joanna Mary Bridger.

Abstract: 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.

Partial Text: The face provides an important template for integrating major sensory inputs from the mouth, nose, eyes, and ears that are then relayed to the adjacent brain. The development and evolution of the face and jaws has been a major driving force in the expansion of vertebrate lineages over recent geological times. Paired jaws have served as critical components for adaptive radiation, and variation in jaw design between species has generated many different vertebrate facial morphologies [1]. Moreover, for humans and many other species, the face provides a fundamental aspect of a person’s individuality, acts as a major component of sexual selection, and serves as the vessel through which our emotions are relayed to others.

The development of the vertebrate face is an intricate process that requires the coordinate growth, morphogenesis, and fusion of separate prominences [2], [3], [4]. Although the face eventually forms an integrated structure, the paired mouse facial prominences – the mandibular, maxillary, and frontonasal – are fated to form distinct functional components of the skeleton, the sensory system, and the respiratory and digestive systems. Variations in the growth properties and derivatives of these prominences have been a major factor driving vertebrate evolution and the expansion of vertebrate species into disparate ecological niches. Furthermore, aberrant development of these prominences is a major factor in human orofacial clefting and other craniofacial birth defects.



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