The department deals with research into the genetic regulation of embryonic development. In our studies, we use tissue-specific gene inactivation (knock‑out) technologies in mice using the Cre-loxP system. We study the functions of Wnt, Shh and FGF signaling pathways and selected transcription factors, e.g. from the Meis, Hand and Pbx families. We focus on the differentiation of neural crest cells and the associated germinal development of cartilage and bone in the craniofacial area and the middle ear. We also study the cellular mechanisms of neural tissue formation derived from neural crest cells. Analyses in mouse models are complemented by experiments in Danio rerio fish embryos. In both experimental organisms, we try to clarify the genetic nature of some human developmental defects.
Meis2 controls skeletal formation in the hyoid region
We identified Meis2 as a critical transcription factor determining embryonic bone formation. In the hyoid bone, we showed that mesenchymal condensation, chondroblast proliferation and their spatial arrangement is driven by transcription factor Meis2.
Elevated proliferation of SOX9 cells in the cartilage primordium of the hyoid bone in Wnt1-Cre2; Meis2 f/f. (A-C’) Frontal frozen sections with orthogonal projections of hyoid regions in controls and Wnt1-Cre2; Meis2 f/f. (D) Quantifications of the percentage of double positive EdU/SOX9 cells in controls and Wnt1-Cre2; Meis2 f/f.
Publication:
Fábik, J., Psutková, V., Machoň, O.: (2022) Meis2 controls skeletal formation in the hyoid region. Frontiers in Cell and Developmental Biology. 28(10): 951063. doi: 10.3389/fcell.2022.951063
MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus
The choroid plexus (ChP) produces cerebrospinal fluid and forms an essential brain barrier. ChP tissues form in each brain ventricle. Epithelial WNT5A is crucial for determining fourth ventricle (4V) ChP morphogenesis and size in mouse. WNT5A, which depends on transcription factors Meis1 and eis2, acts locally to activate non-canonical WNT signaling via ROR1 and ROR2 receptors.
WNT5A signaling in the embryonic ChP epithelium. Epithelial WNT5A, production of which is under direct regulatory control of the transcription co-factor MEIS1, stimulates in an autocrine manner the transmembrane receptors ROR1 and ROR2. Their activation leads to the activation of DVL2 and DVL3.
Publication:
Kaiser, K., Jang, A., Kompanikova, P., Lun-Melody, P., Procházka, J., Machoň, O., Dani, N., Procházková, M., Laurent, B., Gyllborg, D., van Amerongen, R., Fame, R.M., Gupta, S., Wu, F., Barker, R.A., Buková, I., Sedláček, R., Kozmik, Z., Arenas, E., Lehtinen, M.K.: (2021) MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus. Development. 148(10): dev192054. doi: 10.1242/dev.192054.
Projects
1. 1. 2022 – 31. 12. 2024
The role of Meis transcription factors in mesenchymal condensations during formation of the cranium