PXD062221

PXD062221 is an original dataset announced via ProteomeXchange.

Title	Evidence that Dmrta2 acts through repression of Pax6 in cortical patterning and identification of a mutation crucial for DNA recognition associated with microcephaly in human
Description	Dmrta2 (also designated Dmrt5) is a transcriptional regulator expressed in cortical progenitors in a caudomedial high/rostrolateral low gradient with important roles at different steps of cortical development. Dmrta2 has been suggested to act in cortex development mainly by differential suppression of Pax6 and other homeobox transcription factors such as the ventral telencephalic regulator Gsx2, which remains to be fully demonstrated. Here we have addressed the epistatic relation between Pax6 and Dmrta2 by comparing phenotypes in mutant embryos or embryos overexpressing both genes in various allelic combinations. We show that Dmrta2 cooperates with Pax6 in the maintenance of cortical identity in dorsal telencephalic progenitors and that it acts as a transcriptional repressor of Pax6 to control cortical patterning. Mechanistically, we show that in P19 cells, Dmrta2 acts as a DNA14 binding dependent repressor on the Pax6 E60 enhancer and that a point mutation that affects its DNA binding properties identified in a consanguineous family leads to agenesis of the corpus callosum, pachygyria, and the absence of the cingulate gyrus. Finally, we provide evidence that Dmrta2 binds components of the NuRD repressor complex and interacts with zinc finger proteins such as Zfp423. Together, our results highlight the importance and conserved function of Dmrta2 in cortical development and provide novel insights into its mechanism of action.
HostingRepository	PRIDE
AnnounceDate	2025-06-30
AnnouncementXML	Submission_2025-06-29_16:15:00.911.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD062221
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marc Dieu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-25 11:26:54	ID requested
⏵ 1	2025-06-29 16:15:01	announced

10.6019/PXD062221;

10.1523/eneuro.0377-24.2025;

Shen X, Anirudhan J, Fatima A, Plant E, Szemes T, Bouveret Z, Keruzore M, Kricha S, Nan X, Sabat, é, San Jos, é A, Bianchin S, Veraghen B, Delhaye LP, Mian BA, Khalid LB, Ali F, Zahra H, Ali A, Toft M, Dieu M, Achouri Y, Li M, Renard P, Van Lint C, Poulard C, Iqbal Z, Bellefroid EJ, in Cortical Patterning and Identification of a Mutation Impairing DNA Recognition Associated with Microcephaly in Human. eNeuro, 12(6):(2025) [pubmed]

submitter keyword: cerebral cortex, neural progenitor, neurogenesis, transcription factor.

Prof Eric J. Bellefroid
contact affiliation	Laboratory of Developmental Genetics, Department of Molecular Biology and ULB Neuroscience Institute (UNI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
contact email	Eric.Bellefroid@ulb.be
lab head
Marc Dieu
contact affiliation	University of Namur - MaSUN
contact email	marc.dieu@unamur.be
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/2025/06/PXD062221

PRIDE project URI

• PRIDE
  1. PXD062221
     1. Label: PRIDE project
     2. Name: Evidence that Dmrta2 acts through repression of Pax6 in cortical patterning and identification of a mutation crucial for DNA recognition associated with microcephaly in human