08. 09. 2023
Single-cell gene expression analysis of developing craniofacial region
Lecturer: Erika Hudáčová, M.Sc. / Department of Developmental Biology
The seminar will take place on 2. 11. 2023 from 2 p.m. in the Turquoise Auditorium of the IEM CAS.
Annotation: In vertebrates, the skull is composed of various skeletal elements originating from cranial neural crest cells (CNCCs). CNCCs are responsible for the formation of the cranium vault, frontonasal prominence, upper and lower jaw, hyoid bone, external ear and middle ear. The morphogenesis of the craniofacial region encompasses a number of processes, from epithelial-mesenchymal induction and mesenchymal condensation to endochondral or intramembranous ossification. However, the molecular and genetic pathways regulating cranial cartilage shaping and growth during embryogenesis are poorly understood.
In our research, we present Wnt1-Cre2, Meis2 conditional knock-out (cKO) mice with several craniofacial bone abnormalities resembling severe human pathologies due to improper molecular mechanisms guiding mesenchymal condensation. Using single-cell RNA sequencing, we further focus on describing the Meis2-dependent gene regulatory network involved in mesenchymal condensation. Comparison of wild-type and Meis2 cKO embryonic stages E12.5 and E13.5 reveals multiple mesenchymal cell types responsible for craniofacial formation. We have identified markers for cell type specification and positional cues in developing craniofacial regions. Furthermore, differences identified in specific cell types governing mesenchymal condensation and endochondral ossification correlate with the phenotype present in Meis2 cKO mice. Our transcriptomics data in Meis2 cKO show elevated expression of the genes involved in ossification, cell-cell adhesion and cell-extracellular matrix contact. Altogether, the identification of hitherto unknown factors controlling the growth and shape of cranial bones may potentially contribute to the mitigation or prevention of human craniofacial abnormalities.