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 progenitor 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 expressed in TG beginning by 18 hours post fertilization (hpf) and persists through the later developmental stage at 48 hpf. In the prdm16 loss-of-function zebrafish, fewer HuC+ TG neurons are present at 24 hpf and 48 hpf, along with reduced overall ganglion size. Live imaging in Tg( sox10 :mRFP; elavl3 :GFP) embryos demonstrates similar numbers of sox10 + cNCCs migrating to the TG region and reduced cell numbers and overall smaller size of TG in prdm16-/- . Acetylated β-tubulin immunostaining shows fewer trigeminal axon projections early and an altered projection pattern by 48 hpf. A reduction in a defined sensory neuron population, p2rx3b + cells displayed a weaker signal and decreased cell number in prdm16-/- TG. Transcriptomic analysis of FACS-isolated sox10 + cranial neural crest cells supported reduced expression of key neurogenic and sensory lineage genes. Finally, in mouse embryos, PRDM16 is expressed in TG neurons, and Prdm16 (csp1/csp1) embryos exhibited reduced TG volume, area and fewer HuC+ neurons at E18.5. CONCLUSION: Together, these data identify Prdm16 as a conserved regulator of trigeminal ganglion growth and sensory neuron differentiation, linking PRDM-family chromatin regulators to the development of the peripheral sensory nervous system.