Home Blog of Signal Transduction Proteases Gamma-secretase Unexpected role of Notch signaling on directing the trophectoderm lineage in the mouse blastocyst

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Unexpected role of Notch signaling on directing the trophectoderm lineage in the mouse blastocyst

 

During mammalian embryogenesis, the first embryonic lineages, the trophectoderm (TE) and the inner cell mass (ICM) are established from cell balstocyst. Several transcriptional factors are key regulators of this initial lineage choice, including OCT4, NANOG, SOX2, and CDX2. The onset of their expression is fluctuant and lineage-restricted, and the mechanism is largely unknown. Rayon et al. showed that Notch signaling plays a key role in mediating TE-specific expression of Cdx2, though interaction with the transcription factor TEAD4. The article was published on Developmental Cell.  

 

The initial lineage choice is believed to regulate by Hippo signaling pathway, which leads to sustained and restricted expression of genes, including Cdx2. The absence of Hippo signaling in outer cells results in nuclear localization of YAP, a transcriptional coactivator which can activate downstream target genes in cooperation with TEAD4, which is critical for the development of TE. In this study, researchers found that Notch signaling is active specifically in outer cells and converge with Hippo pathway on Cdx2 for its activation in the trophectoderm. Forced activation of Notch signaling converts blastomeres to the trophectoderm. The findings reveal an unexpected role for Notch signaling in mammalian embryogenesis. 

 

Reference:
Dev Cell. 2014 Aug 25;30(4):410-22.

Related Products

Cat.No. Product Name Information
S1575 RO4929097 RO4929097 (RG-4733) is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.

Related Targets

Gamma-secretase Beta Amyloid