Enhancer remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm.

ABSTRACT: The molecular mechanisms that drive essential patterning events in the mammalian embryo remain poorly understood. Analysis of transcription factor expression kinetics at peri-gastrulation stages of development suggest Otx2 as a candidate regulator of the definitive endoderm, the precursor of all gut-derived organs. Accordingly, timed OTX2 depletion in gastruloids or during directed differentiation results in abnormal definitive endoderm specification in mouse and human, characterized by altered expression of components and transcriptional targets of the canonical WNT signaling pathway, perturbed adhesion and migration programs, and de-repression of regulators of other lineages. These defects cumulate in impaired foregut formation. Mechanistically, OTX2 is required to activate a subset of e

SUBMITTER: Ee LS 

PROVIDER: S-EPMC12489875 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature