Regulatory mutants of the Tbx1 gene alter transcription programs of lineage determination and patterning in early mesoderm.
Allegretti, S.; Lanzetta, O.; Bilio, M.; Ferrentino, R.; Salerno, P.; Zoppoli, P.; Merla, G.; Angelini, C.; Baldini, A.
Show abstract
The Tbx1 gene is haploinsufficient in mice and in humans, where it causes a DiGeorge syndrome phenotype characterized by developmental deficits of the pharyngeal apparatus. TBX1 plays a critical role in the differentiation and regionalization of the cardiopharyngeal mesoderm lineage and its derivatives. Nevertheless, its regulation is incompletely understood. Here we used a combination of computational and wet-lab approaches to identify regulatory sequences of the Tbx1 gene, and we use single-cell molecular analysis as a read-out and to establish the consequences of their deletion. Results revealed a cluster of regulatory sequences with at least three distinct elements. Elimination of the entire cluster caused a near shut down of the gene, while individual deletions had milder, quantitative effects. Transcriptomic analyses of the deletion mutants revealed the down regulation of genes related to cardiopharyngeal lineage specification and, more surprisingly, up regulation and anteriorization of genes related to embryonic patterning, thereby providing a rationale for the severe dysmorphogenesis of the posterior pharyngeal apparatus observed in Tbx1 mutant mice.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis. 93%
- The atypical RNA-binding protein TAF15 regulates dorsoanterior neural development through diverse mechanisms in Xenopus tropicalis. 93%
- DUX is a non-essential synchronizer of zygotic genome activation 92%
Similar papers in this journal
- Tbx1 and Foxi3 genetically interact in the third pharyngeal pouch endoderm required for thymus and parathyroid development 93%
- Multilevel regulation of the glass locus during Drosophila eye development 93%
- Expanding the fly eye gene regulatory network: from Drosophila to the hoverfly Episyrphus balteatus. 92%
Similar papers in this journal
- A hypomorphic mutation in Pold1 disrupts the coordination of embryo size expansion and morphogenesis during gastrulation 93%
- Conserved roles of GATA4 and its target gene TBX2 in regulation of human cardiogenesis 93%
- Segregation of brain and organizer precursors is differentially regulated by Nodal signaling at blastula stage 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.