Biology subjects

Wheeler, G. N. N.

Publications and source records attributed to Wheeler, G. N. N..

2 recordsLinked to original sources

bioRxiv2026

MicroRNA miR-219 is required for neural border and neural crest development in Xenopus neurulas

Neural crest (NC) multipotent stem cells give rise to many tissues including most of the peripheral nervous system, pigment cells and the craniofacial mesenchyme and skeleton. During gastrulation and early neurulation, cranial NC cells are specified in the ectoderm territory located between the anterior neural plate ectoderm and the future pre-placodal and lateral non-neural ectoderm. At the end of neurulation, NC cells undergo an epithelial-to-mesenchymal transition and migrate to various locations in the developing embryo where they differentiate. While the fine-tuning of NC specification is increasingly being elucidated, many questions remain, including how microRNAs may govern expression of gene programs during these processes. MicroRNAs are short non-coding 20-22 nucleotides-long RNAs which regulate gene expression through post-transcriptional repression. We have identified miR-219 as a candidate regulator of Xenopus NC development. Here, miR-219-dependent molecular pathways were investigated by morpholino knock-down and reveal NC phenotypes. The development of the NC and adjacent ectoderm was evaluated using whole mount in situ hybridization of key markers (pax3, zic1, xhe2, sox10, snai2, sox2), alcian blue cartilage staining, phenotype analysis, RNA sequencing of microdissected dorsal ectoderm and microRNA rescue experiments. While neural induction is mainly unaffected, miR-219 depletion alters gene expression programs associated with neural border development, resulting in loss of NC specification. HighlightsO_LImiR-219 depletion expands the neural border territory and disrupts neural crest specification. C_LIO_LImiR-219 depletion phenotypes are rescued with miRNA mimics. C_LIO_LImiR-219 morphant neural border expansion is rescued by pax3 depletion. C_LIO_LIRNA-seq reveals specific gene program modulation in miR-219 morphant neural crest. C_LIO_LImiR-219 is predicted to directly downregulate the neural gene Hes5.3. C_LI

developmental biology↗

bioRxiv2025

MicroRNA miR-196a controls neural crest patterning by repressing immature neural ectoderm programs in Xenopus embryos.

HighlightsmiR-196a promotes Neural Crest development: O_LIRNA sequencing of the developing neural border and neural crest reveals miR-196a-dependent gene programs. C_LIO_LImiR-196a represses early neural plate programs and reduces pluripotency gene expression. C_LIO_LImiR-196a may directly control neural crest gene sox10 in vivo. C_LI Neural crest (NC) cells form a multipotent stem cell population specified during neurulation, which undergo an epithelial-to-mesenchymal transition (EMT) and migrate extensively in the developing embryo, to generate numerous tissues and cell types including the craniofacial skeleton, the peripheral nervous system and pigment cells. The genetic and molecular details of NC specification are governed by a complex, yet still partially understood gene regulatory network (NC-GRN). In particular, the precise function of microRNAs (miRNA) in this network remains poorly characterized. miRNAs are short non-coding 20-22 nucleotides long RNAs, which control gene expression through post-transcriptional repression. Since miRNA-196a is expressed in the developing neural and NC cells of Xenopus laevis embryos, we here investigated miR-196a function in the NC-GRN, by knocking-down its expression using antisense morpholinos. Depletion of miR-196a revealed major NC and craniofacial phenotypes. These defects were preceded by the perturbed expression of key neural, neural border and NC markers such as sox2/3, zic1/3, pax3, sox10 and snail2. Using RNA sequencing of individual neural border and NC explants, we have identified a signature of genes up- and down-regulated by miR-196a and validate these with rescue experiments using a miRNA mimic. Our study identifies miR-196a as a key actor of early patterning in the dorsal ectoderm, balancing the extent of immature neural plate progenitors with NC and placode specification, while also promoting neuron differentiation within the neural plate.

developmental biology↗