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Hox Regulation of Neural Crest Cells during Craniofacial Development
Author(s) -
Pushel Irina,
Krumlauf Robb
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.778.2
Subject(s) - hox gene , cranial neural crest , biology , enhancer , genetics , craniofacial , neural crest , transcription factor , microbiology and biotechnology , population , phenotype , gene , computational biology , demography , sociology
Craniofacial structures are shaped by the formation, migration, and differentiation of cranial neural crest cells (cNCCs) in the developing embryo. Many craniofacial defects are caused by misregulation in this embryonic cell population. Recent work has identified key components of the gene regulatory network (GRN) responsible for cNCC development, but there remain gaps in our knowledge. One such example is the Hox family of genes, which are known to pattern subsets of cNCCs and show jaw, ear, and palate defects when misexpressed, yet whose role in the GRN remains unknown. We study mouse embryogenesis to identify which factors Hox genes regulate throughout cNCC development and determine the mechanism by which they contribute to the identity of cNCC derivatives. To approach this question, we use RNAseq to compare the transcriptomes of Hox ‐positive and Hox ‐negative cNCCs and generate a candidate list of genes that are potential Hox targets. We identified several genes known to be involved in the cNCC GRN, allowing us to begin integrating the Hox genes into this network, as well as novel targets that appear to be significant in craniofacial development. To identify the regulatory mechanisms that affect Hox targets, we use ATAC‐seq to compare chromatin accessibility between cNCC subpopulations and identify enhancers that may modulate the expression of genes downstream of the Hox family. We are working to systematically test the more promising targets through perturbation, expression analysis in mutants, and reporter assays to validate direct regulatory interactions between Hox genes and other key factors of the GRN, particularly as they relate to differences between subpopulations of cNCCs that give rise to distinct derivatives. Expanding current knowledge of the GRN governing cNCC development in this manner establishes a greater foundation for future work on this cell population. Moreover, the integration of the Hox genes, as one specific example, into this framework will develop a more precise understanding of the developmental dynamics responsible for craniofacial defects and can ultimately inform clinical approaches to the etiology and treatment of these defects. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .