Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
Dev Biol 2023 Mar 01;495:42-53. doi: 10.1016/j.ydbio.2022.11.010.
Show Gene links Show Anatomy links

Mink1 regulates spemann organizer cell fate in the xenopus gastrula via Hmga2.

Colleluori V , Khokha MK .

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 regulates canonical Wnt signaling to define the cell fates of the Spemann Organizer and the Left-Right Organizer, a ciliated structure that breaks bilateral symmetry in the vertebrate embryo. To identify Mink1 targets, we applied an unbiased proteomics approach and identified the high mobility group architectural transcription factor, Hmga2. We report that Hmga2 is necessary and sufficient for regulating Spemann's Organizer. Indeed, we demonstrate that Hmga2 can induce Spemann Organizer cell fates even when β-catenin, a critical effector of the Wnt signaling pathway, is depleted. In summary, we discover a transcription factor, Hmga2, downstream of Mink1 that is critical for the regulation of Spemann's Organizer, as well as the LRO, defining a plausible mechanism for CHD.

PubMed ID: 36572140
PMC ID: PMC10116378
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: ctnnb1 dand5 foxj1 foxj1.2 gsc hmga2 mink1 nodal1 nodal3.1 nodal3.4 nucks1 pitx2 rpl30 tdgf1
GO keywords: Wnt signaling pathway involved in heart development [+]
Antibodies: Ctnnb1 Ab9 Gapdh Ab5
gRNAs referenced: hmga2 gRNA1 hmga2 gRNA2 mink1 gRNA1 mink1 gRNA2 mink1 gRNA3

Disease Ontology terms: congenital heart disease

Article Images: [+] show captions