Deciphering Heterogeneity Of Human Molar Developmental Dental Lamina Anteroposterior Expression

To address this critical knowledge gap, the mechanisms driving the distal extension of the continuous dental lamina (DL)—the developmental foundation for sequential molar formation—remain undefined in human embryogenesis. This article conducted an investigation utilizing tooth germ tissues obtained from human fetuses at 21-31 weeks of gestation (from aborted fetuses)( Ethic number:202203062).The experimental approach encompassed single-cell RNA sequencing (scRNA-seq), computational 3D reconstruction, multiplex immunofluorescence staining, and quantitative fluorescence analysis. The first molar's DL was found to be positioned lingually and to extend distally during development.ScRNA-seq profiling identified a distinct DL epithelial subpopulation, with subsequent pseudotime analysis and immunofluorescence validation revealing a striking proximal-distal molecular gradient - marked by predominant expression of SOX2, DLX5,SOX9 and KRT13 in proximal DL regions, contrasting with RUNX2 dominance in distal mesenchymal compartments.By bioinformatics analyses, including enrichment profiling and cell-cell communication network reconstruction, suggest JUNB+ DL cells as key regulatory elements potentially governing distal DL elongation through FGF signaling pathways. This study establishes a three-dimensional model of human molar dental lamina morphogenesis, reveals proximal-distal molecular heterogeneity, and uncovers region-specific molecular signatures. The analysis of the expression profile and the exploration of the mechanism can provide a scientific basis for the prevention and treatment of dental developmental disorders and diseases.