The human nervous system emerges during early embryogenesis through coordinated, self-organizing differentiation of peripheral and central lineages. A key event in this process is the emergence of neural crest from the dorsal neural tube, which gives rise to major peripheral nervous system (PNS) structures. However, current in vitro models face challenges in recapitulating this process, limiting mechanistic insights into human central-peripheral neurogenesis. Here, we report a method for generating human peripheral-central dual neural organoids (hPCOs), a self-organizing organoid system that recapitulates the co-development of peripheral sensory ganglia and dorsal spinal cord. Using hPCOs, we uncover an unexpected bidirectional role of Wnt signaling in orchestrating peripheral and central fate determination. Modeling with hPCOs reveals nociceptor defects in human congenital insensitivity to pain. Furthermore, integrating hPCOs with image analysis enables the visual assessment of teratogenic risks. Together, hPCOs provide a physiologically relevant platform for investigating human self-organized central nervous system (CNS)-PNS co-development, disease mechanisms, and drug discovery.

Jha et al.[1] show that confined melanoma cells establish migratory polarity by restricting EGFR mobility at the bleb rear, using CD44 and ezrin-radixin-moesin (ERM) proteins as diffusion barriers rather than directional cues. These findings reveal a divergence from mesenchymal migration and prove that confinement alone can polarize a migrating cell.

Embryonic diapause is a reversible dormant state that allows mammalian blastocysts to survive periods of environmental or metabolic stress. In this issue of Developmental Cell, Furlan et al.[1] report that Nodal/Smad2 signaling sustains diapause by repressing Pparg-driven lipid storage in the blastocyst.

In this issue of Developmental Cell, Matsuda et al.[1] and Nakanoh et al.[2] reveal that global protein turnover rate controls species-specific developmental clocks. Their findings demonstrate how translation and degradation rates regulate embryonic timing, raising the possibility that cells directly sense developmental progression through their metabolic state.

Expression of Pax7 has been widely used as a hallmark of muscle stem cell identity, and genetic deletion of Pax7 compromises skeletal muscle regeneration. In this issue of Developmental Cell, Gioftsidi, Hayashi et al. use lineage-tracing approaches to report that other skeletal muscle cell types also express Pax7.[1].

The circadian clock maintains a nearly constant pace across a wide range of temperatures in plants. In this issue of Developmental Cell, He et al. reveal how condensation of the morning clock protein PRR9 and its protein-protein interactions mediate high temperature sensing and adjust the pace of the circadian clock.

Invariant natural killer T (iNKT) cells acquire effector identity during thymic development, yet how metabolic and signaling programs regulate iNKT cell fate remains unclear. In this issue of Developmental Cell, Li et al.[1] elucidate that the VHL-HIF axis with HIF1α and HIF2α modulates survival and differentiation of iNKT cells.

Rooted in place, plants must continually balance adaptation and cell death under environmental stress. In this issue of Developmental Cell, Yang et al. demonstrate that NAC089, an ER-localized transcription factor, acts as a molecular switch that determines these alternative outcomes under different environmental conditions.

Cellular senescence is one of the best-studied biological programs, yet it continues to reveal unexpected aspects. In this issue of Developmental Cell, Durik et al.[1] describe how senescent cells shed large cytoplasmic fragments that promote their survival and may represent a mechanism of communication with neighboring cells.

Transcription involves initiation, pausing, elongation, and termination. Suppressor of Ty5 (SPT5) regulates promoter-proximal pausing and elongation, but how it orchestrates both steps during dynamic developmental changes in gene expression remains unclear. Here, using rapid optogenetic depletion in Drosophila embryos, we uncover different consequences of SPT5 removal at different developmental stages. In early embryos, SPT5 depletion causes a shift of RNA polymerase II (Pol II) from the canonical pausing site to the +1 nucleosome, which is strongly positioned. In late embryos, SPT5 depletion similarly reduces pausing at the canonical site, but the transcriptional machinery can overcome the +1 nucleosome-which appears more labile at this time point-moving into the gene body. This results in lethality and both up- and downregulation of expression, depending on the balance between Pol II entering the gene body and defective elongation. This is intensified for genes naturally increasing or decreasing their expression, indicating that SPT5 contributes to fine-tuning dynamic expression changes.

Salt stress severely limits rice productivity, yet the genetic basis of natural variation and the underlying mechanism remain poorly understood. Here, through genome-wide association analysis and fine-mapping, we identify a major quantitative trait locus (QTL) gene, Tolerance to Salt 1 (TOLS1), that negatively regulates salt tolerance in rice. Overexpression of TOLS1 increases salt sensitivity, whereas loss of function enhances salt tolerance. TOLS1 interacts with the small guanosine triphosphatase (GTPase) OsRacB and enhances its GTPase activity, thereby attenuating salt-induced cytosolic Ca[2+] elevation. We further identify a natural coding variation, SNP9 (+1018 A/G), in TOLS1 that contributes to functional divergence, with the TOLS1[A] allele exerting a stronger negative effect on salt tolerance than TOLS1[G]. Collectively, these findings reveal that natural variation in TOLS1 modulates OsRacB-Ca[2+] signaling and thereby contributes to salt tolerance divergence in rice. This study provides mechanistic insight into how TOLS1 allelic variation regulates salt signaling and offers a potential target for molecular design breeding.

Cellular senescence is a state of stable arrest and secretion linked to aging and disease. Here, we identify that senescent cells dispose of large fragments through cell-to-cell adhesion, which we term "senescent-cell adhesion fragments" (SCAFs). Found in many senescent states, including human and mouse cells, and mouse tissues, SCAFs lack nuclear material but contain organelles, including damaged mitochondria. Disrupting adherens junctions decreases SCAF formation but induces senescent-cell death, due to an inability to shed damaged mitochondria. Live imaging and proteomics show that SCAFs ultimately rupture, releasing a complex proteome, including damage-associated molecular patterns (DAMPs) and proteins linked to neurodegenerative disease. Functionally, SCAFs activate wound-healing and cancer-related programs, promoting migration and invasion. Immunostaining also reveals amyloid-like material in senescent cells that can be externalized through fragmentation. Altogether, these findings identify a feature that facilitates senescent cell survival but also externally deposits damaged intracellular contents, with implications for cancer and neurodegeneration.

In flowering plants (angiosperms), the Polygonum-type embryo sac accounts for approximately 70% of the female gametophytes. It contains three antipodal cells, one central cell, one egg cell, and two synergid cells. Apart from the female gamete cells, the synergid cells play a key role in sexual reproduction. This review traces the origin and research history of synergid cells and summarizes the latest research progress in understanding their core functions in the angiosperm-specific siphonogamy. In particular, we discuss the diverse functions of synergid cells in pollen tube guidance, pollen tube reception, and fertilization recovery. We highlight how angiosperms guarantee fertility by regulating the timing and sequence of the synergid cell degeneration and persistence. Moreover, we discuss important unresolved scientific questions in synergid cell research and provide an outlook on future research directions.

Organs comprise diverse cell types originating from shared or distinct lineages. During embryogenesis, mesodermal Pax7[+] progenitors give rise to skeletal muscle as well as non-muscle lineages like dermis and adipocytes. Here, we asked whether Pax7[+] cells retain multipotency during early postnatal limb muscle growth. Lineage tracing in neonatal mice revealed unexpected early postnatal plasticity, yielding multiple non-myogenic lineages, including a previously unrecognized subpopulation of fibro-adipogenic progenitors, termed Pax7[FAPs]. Using mouse models, we demonstrated that Notch signaling primes neonatal Pax7[+] cells toward a fibrogenic molecular identity, biasing their trajectory away from myogenesis. Long-term tracing confirmed that neonatally generated Pax7[FAPs] persist into adulthood. Furthermore, adult muscle injury triggered de novo generation of Pax7[FAPs], which exhibited higher proliferative capacity than resident stromal cells. This postnatal Pax7[+] multipotency reveals an additional cellular contribution to muscle development and regeneration.

Intratumoral heterogeneity fuels cancer progression and therapy resistance, yet the cooperative mechanisms between distinct subclones remain poorly defined. Here, we uncover a tumor-promoting form of cell competition wherein malignant clones hijack interclonal Hedgehog (Hh) and Wnt signaling to convert competitive pressure into a pro-tumorigenic force. In Drosophila, we find that Pp1-87B depleted, RAS-mutant "loser" cells undergo Hh-mediated apoptosis while secreting Wingless (Wg). This paracrine Wg signal hyperactivate β-catenin in neighboring RAS "winner" clones, reprogramming them into invasive super-competitors. This mechanism is conserved in human pancreatic ductal adenocarcinoma (PDAC), where PPP1CA loss in KRAS-mutant cells induces analogous Hh-Wnt synergy, accelerating tumor growth in mouse xenograft models and correlating with clonal selection in patient specimens. Our study elucidates a paradoxical role for cell competition in intratumoral heterogeneity, where distinct tumor clones across species exploit conserved developmental signaling pathways to fuel malignancy. These findings establish interclonal communication as a critical driver of tumor ecosystem dynamics and identify Hh-Wnt crosstalk as a promising therapeutic vulnerability in heterogeneous cancers.