hlh-14/Ascl1 acts as a proneural factor during natural and induced epithelial-to-neuron transdifferentiation in vivo
Abstract
Understanding how fully differentiated cells can change their identity remains a fundamental question in developmental and regenerative biology. C. elegans offers unique in vivo models at a single-cell resolution, notably natural K-to-DVB transdifferentiation event, where a rectal cell converts into a neuron during postembryonic development. Our previous work showed that complex molecular events involving sox-2 and Wnt signalling led to the erasure of the rectal identity and the triggering of the lim-6 DVB terminal selector. However, lim-6 does not account for all DVB neuronal re-differentiation. Here we show that hlh-14, the C. elegans ortholog of Ascl1, acts as a proneural factor during the K-to-DVB natural transdifferentiation. hlh-14 acts downstream of Wnt signalling, and is required for the expression of lim-6 and neuronal redifferentiation. Moreover, overexpression of the sole hlh-14 reprograms additional rectal cells into neurons, while revealing lineage biases in reprogramming competence. Together, our results identify hlh-14 as a key determinant of both natural and induced epithelial-to-neuron transdifferentiation in vivo, linking developmental plasticity to induced reprogramming and revealing the deep conservation of Ascl1 reprogramming abilities from worms to mammals.
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BibTeX
@misc{cury2026hlh14ascl1,
title = {{hlh-14/Ascl1 acts as a proneural factor during natural and induced epithelial-to-neuron transdifferentiation in vivo}},
author = {Jeanne Cury and Louise Bucher and Claudia Riva and Sophie Jarriault},
howpublished = {HAL},
year = {2026},
month = oct,
url = {https://hal.science/hal-05789152v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - hlh-14/Ascl1 acts as a proneural factor during natural and induced epithelial-to-neuron transdifferentiation in vivo
AU - Jeanne Cury
AU - Louise Bucher
AU - Claudia Riva
AU - Sophie Jarriault
PY - 2026
DA - 2026/10/09
PB - HAL
UR - https://hal.science/hal-05789152v1
AB - Understanding how fully differentiated cells can change their identity remains a fundamental question in developmental and regenerative biology. C. elegans offers unique in vivo models at a single-cell resolution, notably natural K-to-DVB transdifferentiation event, where a rectal cell converts into a neuron during postembryonic development. Our previous work showed that complex molecular events involving sox-2 and Wnt signalling led to the erasure of the rectal identity and the triggering of the lim-6 DVB terminal selector. However, lim-6 does not account for all DVB neuronal re-differentiation. Here we show that hlh-14, the C. elegans ortholog of Ascl1, acts as a proneural factor during the K-to-DVB natural transdifferentiation. hlh-14 acts downstream of Wnt signalling, and is required for the expression of lim-6 and neuronal redifferentiation. Moreover, overexpression of the sole hlh-14 reprograms additional rectal cells into neurons, while revealing lineage biases in reprogramming competence. Together, our results identify hlh-14 as a key determinant of both natural and induced epithelial-to-neuron transdifferentiation in vivo, linking developmental plasticity to induced reprogramming and revealing the deep conservation of Ascl1 reprogramming abilities from worms to mammals.
ER -