PXD028827

PXD028827 is an original dataset announced via ProteomeXchange.

Title	Mink1 Kinase Regulates Dorsal Mesodermal Cell Fate in the Xenopus Gastrula via HMGA2
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-05-22
AnnouncementXML	Submission_2024-05-22_01:16:49.063.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028827
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vaughn Colleluori
SpeciesList	scientific name: Xenopus tropicalis; NCBI TaxID: 8364;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-29 01:33:06	ID requested
⏵ 1	2024-05-22 01:16:49	announced

10.6019/PXD028827;

10.1016/j.ydbio.2022.11.010;

Colleluori V, Khokha MK, Mink1 regulates spemann organizer cell fate in the xenopus gastrula via Hmga2. Dev Biol, 495():42-53(2023) [pubmed]

submitter keyword: left right patterning, Beta catenin, Xenopus, HMGA2,MINK1, Wnt signaling, Spemann organizer, congenital heart disease, gastrulation

Mustafa Khokha
contact affiliation	Yale University Department of Pediatrics and Genetics Yale School of Medicine
contact email	mustafa.khokha@yale.edi
lab head
Vaughn Colleluori
contact affiliation	Yale University
contact email	vaughn.colleluori@yale.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD028827

PRIDE project URI

• PRIDE
  1. PXD028827
     1. Label: PRIDE project
     2. Name: Mink1 Kinase Regulates Dorsal Mesodermal Cell Fate in the Xenopus Gastrula via HMGA2