Mink1 Kinase Regulates Dorsal Mesodermal Cell Fate in the Xenopus Gastrula via HMGA2

ABSTRACT: Congenital Heart Disease (CHD) is the most common birth defect and leading cause of infant mortality, yet molecular mechanisms explaining CHD remain mostly unknown. Sequencing studies are identifying CHD candidate genes at a brisk rate including MINK1, a serine/threonine kinase. However, a plausible molecular mechanism connecting CHD and MINK1 is unknown. Here, we reveal that mink1 is required for proper heart development due to its role in left right patterning. mink1 defines the cell fates of the Left-Right Organizer (LRO), a ciliated structure in the posterior mesoderm that breaks bilateral symmetry in vertebrate embryos. To identify mink1 targets, we applied an unbiased proteomics approach and identified the transcription factor, HMGA2. HMGA2 is necessary and sufficient for specifying Spemann’s Organizer, which can neuralize the ectoderm and dorsalize the mesoderm. Indeed, we demonstrate that HMGA2 is downstream of catenin, a critical effector of the Wnt signaling pathway that is well known to induce Spemann Organizer cell fates. In summary, we discover a transcription factor, HMGA2, that is downstream of mink1 that is critical for the specification of Spemann’s Organizer as well as the LRO defining a plausible mechanism for CHD.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Xenopus Tropicalis

TISSUE(S): Embryo, Whole Body

SUBMITTER: Vaughn Colleluori  

LAB HEAD: Mustafa Khokha

PROVIDER: PXD028827 | Pride | 2024-05-22

REPOSITORIES: Pride