Many cartilage and skeletal elements in the cranium arise from neural crest cells. These multipotent cells are generated in the neural plate border, migrate out of the neural tube into many regions of the developing embryo and differentiate into various cell types such as cranial cartilage and bones, peripheral nerves and glia, pigment cells or connective tissues. Cranial neural crest-derived mesenchyme condensates before differentiating into chondrocytes or osteoblasts. However, genetic and cellular mechanisms regulating the cartilage shape and growth are poorly understood. We employ mouse conditional knock-out of the transcription factor Meis2 using Wnt1-Cre2 in which several craniofacial bones are malformed during embryogenesis due to improper mesenchymal condensations. We will use spatial transcriptomics, RNA-seq, in situ hybridization or immunohistochemistry to describe Meis2- dependent gene regulatory network and hitherto unknown factors controlling precise growth and enormous variety of shapes of cranial bones.
We plan to elucidate cellular and genetic mechanisms determining mesenchymal condensations during formation of cranial cartilage and bones. We use mouse knock-outs of transcription factors in the neural crest and spatial transcriptomics to elucidate principles of cranial bones growth and shaping.