Abstract Background The trigeminal ganglion (TG) integrates sensory input from the face and jaw and is derived from two embryonic cell populations: neural crest and cranial placode. These populations interact during TG development to coordinate specification, differentiation, and organization, but the molecular characteristics of the heterogeneous cell populations within the developing TG remain poorly defined. Results We performed single‐cell RNA‐sequencing (scRNA‐seq) of chick TG at HH17, generating a high‐resolution dataset of ~87,000 cells representing diverse neuronal and non‐neuronal populations. Subclustering and RNA velocity analysis of Isl1 + neuroblasts resolved distinct developmental trajectories associated with neural crest‐ and cranial placode‐derived populations converging toward neuronal differentiation. A Sox10 + neural crest‐associated population progressively acquired neuronal characteristics, while a distinct placode‐associated trajectory exhibited loss of epithelial gene expression during neuronal maturation. We additionally identified lineage‐enriched long non‐coding RNAs (lncRNAs), including MIR137HG , which was strongly enriched in Isl1 + neuroblasts and spatially validated across TG development. Conclusions Our study provides a single‐cell atlas of the developing chick TG that resolves transcriptional heterogeneity and developmental states within its neural crest‐ and placode‐derived populations. These data identify candidate molecular signatures associated with sensory neuronal differentiation and provide a resource for investigating the mechanisms governing trigeminal gangliogenesis.
Abstract Background Cranial neural crest cells (cNCC) generate craniofacial cartilage, bone, and peripheral neurons and glia, and birth defects arise when the cartilage/neuronal/glial progenitors fail to differentiate. PRDM16 is a transcriptional regulator containing both zinc‐finger and SET domains, implicated in craniofacial development and orofacial clefting, but its role in cranial sensory ganglion formation has not been defined. Results Here, we demonstrate that prdm16 is required for trigeminal ganglion (TG) assembly and sensory neurogenesis from cranial neural crest lineages. In zebrafish, prdm16 is highly expressed in TG and sox10‐ positive neural crest cells, beginning by 18 h post fertilization (hpf) and persists through the later developmental stage at 48 hpf. Similarly, Prdm16 expression is also found in the mouse TG neurons at embryonic day (E) 18.5. In the prdm16 loss‐of‐function zebrafish, fewer HuC+ TG neurons are present at 24 hpf and 48 hpf, resulting in reduced overall ganglion volume and area. Live imaging in Tg( sox10 :mRFP; elavl3 :GFP) embryos demonstrates that similar numbers of sox10 + cNCCs migrate to the TG region in wildtype and mutants; however, reduced trigeminal ganglion cell numbers and area are observed in prdm16 −/−. Acetylated β‐tubulin immunostaining shows fewer trigeminal axon projections early and an altered projection pattern by 48 hpf. p2rx3b + defined sensory neuron population displayed reduced signal intensity and decreased cell number in prdm16 −/− TG. Transcriptomic analysis of FACS‐isolated sox10 + cranial neural crest cells shows reduced expression of key neurogenic and sensory lineage genes. Finally, the role of PRDM16 in trigeminal neurogenesis is conserved across vertebrates: Prdm16 csp1/csp1 mutant mouse embryos also exhibited reduced TG mediolateral diameter, overall area, and fewer HuC+ neurons at E18.5 compared to control. Conclusion Together, these data identify Prdm16 as a conserved regulator of trigeminal ganglion growth and sensory neuron differentiation, linking PRDM‐family of chromatin regulators to the development of the peripheral sensory nervous system.
Abstract Renal diseases such as acute and chronic kidney disease cause loss of nephrons and kidney function, often leading to renal failure. Current treatments like dialysis and transplantation only manage symptoms and extend survival for a few years. Regenerative medicine offers promising approaches for repairing and regenerating renal tissue by targeting underlying disease mechanisms. For this narrative review, relevant original research articles and review articles were retrieved from online databases such as PubMed, Google Scholar, and ScienceDirect by using relevant keywords such as “renal regeneration,” “kidney organoids,” “stem cell therapy,” “gene therapy,” “extracellular vesicles,” and “tissue engineering.” The literature search focused primarily on articles published between 2020 and 2026 to discuss the recent advancements in regenerative approaches for renal disease. Recent advances in regenerative medicine have identified therapies such as stem cells, gene therapy, CRISPR‐Cas9, extracellular vesicles, and kidney organoids that promote nephron regeneration, improve vascularization, regulate inflammation, and restore kidney function. This review highlights the cellular and molecular mechanisms underlying renal damage, recent advances in regenerative medicine, and the key challenges and future directions for the safe and effective use of regenerative medicine in treating renal diseases.
Abstract Background Precise control of DYRK1A dosage is essential for embryonic development, including craniofacial morphogenesis. While LZTS2 is among the most consistently identified DYRK1A‐interacting proteins, its roles in embryonic development remain incompletely understood, and its potential contribution to craniofacial development has not been examined. Xenopus laevis was used to test the role of LZTS2 in craniofacial development and its functional relationship with DYRK1A. Results Lzts2 and Dyrk1a showed overlapping expression during craniofacial development, with both proteins present in developing facial tissues. Knockdown of Lzts2 disrupted craniofacial morphogenesis and reduced expression of craniofacial genes. These phenotypes closely resembled those caused by decreasing Dyrk1a function. Sub‐phenotypic reductions of Lzts2 and Dyrk1a synergized to produce craniofacial defects, while partial reduction of Lzts2 attenuated aspects of the phenotype caused by Dyrk1a overexpression. Comparative analysis of human phenotypes associated with copy number gains of LZTS2 and DYRK1A revealed striking overlap, consistent with a potential functional interaction between these genes in humans. Conclusions These findings identify Lzts2 as a previously unrecognized regulator of craniofacial development and support a functional interaction with Dyrk1a during embryogenesis. Modulating LZTS2 or related regulatory partners may provide a strategy to selectively tune DYRK1A‐dependent developmental pathways.
Neural crest cells are multipotent, migratory stem-like cells essential for vertebrate development that contribute broadly to many tissues including the craniofacial skeleton, peripheral nervous system, and pigment-producing cells. Their development progresses through phases of induction, specification, delamination, migration, and differentiation. Importantly, advancement through these phases requires detecting and responding to extracellular cues through the plasma membrane. While the gene regulatory networks and the signals that govern neural crest development are well characterized, plasma membrane lipid composition as a regulatory layer controlling these transitions remains underexplored. Despite technical limitations in quantitative lipid measurements from vertebrate embryos, genetic and molecular studies have inferred roles of key lipid metabolites. Here we review how membrane lipid metabolism and composition regulate neural crest behavior, focusing primarily on sphingolipids, cholesterol, and lipid raft domains. We examine how morphogen signaling is modified and organized by lipids, how modulating lipid content alters the biophysical state of the neural crest plasma membrane, and the deleterious effects of dysregulated lipid metabolism in neurocristopathies. Drawing parallels to other developmental and disease contexts, we highlight membrane lipid metabolism as a critical frontier in neural crest biology with broad implications for understanding developmental mechanisms and congenital disorders.
