Biology subjects

Greenfeld, H.

Publications and source records attributed to Greenfeld, H..

3 recordsLinked to original sources

bioRxiv2026

Dynamic polyadenylation safeguards developmental trajectories during paused embryogenesis

Embryonic pausing, including forms of diapause, enables development to be reversibly suspended during adverse conditions, but how paused embryos preserve cell fate patterning remains unclear. Using zebrafish, we show that developmental pausing results in the temporary collapse of Wnt, BMP, FGF, and Nodal signaling gradients, despite broad preservation of cell identity at the transcriptional level. In parallel, pausing induces a dormancy-enriched gene expression program (DEEP), which includes the non-canonical poly(A) polymerase tent5ba. Tent5ba promotes survival through pausing, sustains DEEP expression, and is required for robust reestablishment of axial patterning upon developmental re-entry. Poly(A)-tail and transcriptional profiling further link tent5ba to the stabilization of mRNA targets associated with robust developmental outcomes, supporting a model in which transcript polyadenylation safeguards patterning fidelity through suspended embryogenesis.

developmental biology↗

bioRxiv2026

BMP signaling during gastrulation pre-patterns the dorsal spinal cord

The classic model of dorsal spinal cord patterning proposes that roofplate-derived BMP patterns dorsal interneuron subtypes in a concentration-dependent manner. However, genetic perturbations of BMP pathway components produce variable effects, challenging this model. Here we implemented single-cell profiling, fate mapping, and mosaic perturbations to determine when BMP signaling patterns dorsal neural fates in vivo. Contrary to the classic model, we demonstrate that dorsal fates are patterned by BMP signaling during gastrulation. Following neural tube formation, BMP signaling continues but plays limited roles in domain specification and maturation. Fate mapping revealed that dorsal progenitors originate from the ventral gastrula, adopting BMP-dependent transcriptional states that prime dorsal neural fate. We propose that dorsal neural fates are initially patterned by gastrulation-stage sources of BMP, prior to roofplate induction.

developmental biology↗

bioRxiv2025

Two parallel lineage-committed progenitors contribute to the developing brain

The hindbrain is a life-sustaining brain region. In one model, a common neural progenitor generates all brain regions. Here our studies of mouse embryos and human pluripotent stem cells (hPSCs) support a different model: two parallel brain progenitors emerge simultaneously during gastrulation, anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (hindbrain progenitor). Not only are they lineage-committed to respectively form forebrain/midbrain vs. hindbrain in vitro, but they also have diverging chromatin landscapes foreshadowing future forebrain/midbrain vs. hindbrain identities. Leveraging these differences, we differentiated hPSCs into hindbrain rhombomere 5/6-specific motor neurons, hitherto difficult to generate in vitro. We postulate the brain is a composite organ emanating from two lineage-restricted progenitors; these dual progenitors may be evolutionarily conserved across 550 million years from hemichordates to mammals.

developmental biology↗