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Single-cell transcriptome profiling reveals developmental trajectory and transcriptional regulatory networks of mouse maxillary prominence

ABSTRACT: During embryonic development of vertebrates, neural crest- derived mesenchymal cells within the maxillary prominences undergo precisely coordinated proliferation and differentiation to give rise to a series of craniofacial structures, such as tooth and secondary palate. However, the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated. Here we combined bulk and single-cell RNA-Seq to comprehensively characterize the transcriptome dynamics during mouse maxillary development from embryonic day (E) 10.5 to 14.5. We identified mesenchymal cell populations that represent different developmental states and inferred their developmental trajectory, demonstrating that a cell fate divergence toward the palatal versus dental mesenchyme lineage occurs at E11.5. We further identified the core transcriptional regulators associated with maxillary cell fate transitions and deduced the gene regulatory networks directed by these factors. We further demonstrated that Foxp1 regulates genes involved in skeletal and cartilage development and is required for efficient osteogenesis. Collectively, our study provides rich resources and important insights for achieving a systems level understanding of craniofacial morphogenesis and abnormality.

ORGANISM(S): Mus musculus

PROVIDER: GSE161143 | GEO | 2023/02/15

REPOSITORIES: GEO

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Project description:Growth and patterning of the face relies on several small buds of tissue, the facial prominences, which surround the primitive mouth. Beginning around E10 of mouse development the prominences undergo rapid growth and morphogenesis. By E11.5 the medial nasal prominences are in close apposition in the midline, as are the maxillary and medial nasal prominences on either side of the developing face. Subsequently, by E12.5 the nasal and maxillary prominences fuse to form a continuous shelf at the front of the face - the primary palate. Individual prominences are associated with specific developmental processes, and this is reflected by patterns of differential gene expression that give the prominences their unique identities. Thus, only the mandibular and maxillary prominences give rise to dentition while the frontonasal prominence has a unique role in olfaction, and the mandibular prominence in taste. We used microarrays to detail the differential gene expression program in each of the mandibular, maxillary, and frontonasal prominences during the key developmental timepoints of E10.0 through E12.5. Experiment Overall Design: Analysis of gene expression during growth and fusion of the facial prominences in the C57BL/6J mouse strain between embryonic (E) day 10.0 and 12.5. At the earliest timepoint, E10, only the mandibular prominence is a distinct entity that can be readily identified and dissected. The frontonasal prominence and the maxillary prominence are very small and not discrete from other components of the head such as the forebrain until E10.5. Analysis of these tissues at earlier timepoints would require laser capture and preamplification steps - techniques that were not used for the later timepoints. Thus samples were isolated from the mandibular prominence at E10.0 and from the mandibular, maxillary and frontonasal prominences of mouse embryos from E10.5 to E12.5, at 0.5 day intervals. In order to obtain sufficient sample for hybridization, each sample represents a pool of between 3 and 48 embryos depending on the timepoint. Specifically, the number of embryos were 40-48 for E10.0 (mandibular prominence only), 24-8 for E10.5, 8-9 for E11.0 and E11.5 and 3-4 for E12.0 and E12.5. Seven replicate samples were taken for each of the later five timepoints in each of the three prominences, with an additional seven samples for the mandibular E10.0 timepoint, for a total of 112 samples.

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Single-cell transcriptome profiling reveals developmental trajectory and transcriptional regulatory networks of mouse maxillary prominence

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