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Identification of evolutionary conserved and diverged regulatory elements of embryonic Msx1 expression among amniote species via 3D-genome analyses and in vivo assays
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DOI：10.1016/j.ydbio.2026.02.006.png)
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Abstract
En 中文
The Msx1 gene encodes a homeobox transcription factor that regulates numerous patterning events during the development of organs such as the limb bud and jaw primordium. In craniofacial development, Msx1 is involved not only in the proximal-distal patterning of the jaw but also in the spatial arrangement of different tooth types along the proximal-distal axis in various mammalian species. Our previous study demonstrated that speciesspecific differences in Msx1 expression within the jaw primordium contribute to the establishment of distinct dental formulas. Although several proximal enhancers responsible for the embryonic Msx1 expression have been identified, it remains unclear whether additional enhancers exist and whether combinations of such regulatory elements contribute to the species-specific Msx1 expression patterns in the developing jaw primordium. In this study, we utilized 4C-seq, a 3D genome conformation technology, to identify genomic regions in close proximity to the Msx1 promoter. Through this analysis, we delineated the topologically associating domain (TAD) encompassing the Msx1 locus. Combined with genomic sequence comparisons and in vivo reporter assays, we identified novel enhancers within this TAD, including elements active in the developing jaw primordia. Notably, some of these enhancers are conserved only in chicken and opossum genomes but are absent in the placental mammals, whereas others derived from mouse and opossum exhibited distinct spatiotemporal patterns in chicken and mouse embryos. This suggests that dynamic cis-regulatory evolution of the Msx1 locus may be responsible for species-specific jaw patterning and tooth arrangements. This study thus provides a valuable framework for understanding the evolutionary dynamics of developmental enhancers that contribute to morphological diversity in vertebrates.
Keywords:
Msx1
Enhancer
3D genome
4C-seq
Jaw development
Opossum
Mouse
Chicken
Journal
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2.1
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393
Citations:
2.2W
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Cited Papers