Santillan, E. M. | Search bioRxiv

bioRxiv2025

Core microRNAs regulate neural crest delamination and condensation in the developing trigeminal ganglion

Cranial neural crest cells (NCCs) undergo dynamic processes during embryonic development, including delamination from the neural tube by epithelial-to-mesenchymal transition (EMT), migration to the periphery, condensation via mesenchymal-to-epithelial transition (MET) and differentiation into structures like the trigeminal ganglion. Here, we identify and characterize the function of a core set of miRNAs involved in these transitions during the formation of the trigeminal ganglion in the chick embryo. We further identify putative targets of miRNAs involved in neural crest EMT and MET. Notably, introducing MET-involved miRNAs into trunk NCCs endows these cells with the ability to condense and differentiate into neurons in vivo in a manner reminiscent of cranial rather than trunk NCCs. Our findings shed light on the intricate regulatory networks governing NCC behavior, positioning miRNAs as key regulatory elements required for migratory transitions and axial level specific differentiation capabilities.

developmental biology↗

bioRxiv2020

A deeply conserved miR-1 dependent regulon supports muscle cell physiology

Muscles are not only essential for force generation but are also key regulators of systemic energy homeostasis1. Both these roles rely heavily on mitochondria and lysosome function as providers of energy and building blocks, but also as metabolic sensors2-4. Perturbations in these organelles or their crosstalk lead to a wide range of pathologies5. Here, we uncover a deeply conserved regulon of mitochondria and lysosome homeostasis under control of the muscle-specific microRNA miR-1. Animals lacking miR-1 display a diverse range of muscle cell defects that have been attributed to numerous different targets6. Guided by the striking conservation of miR-1 and some of its predicted targets, we identified a set of direct targets that can explain the pleiotropic function of miR-1. miR-1-mediated repression of multiple subunits of the vacuolar ATPase (V-ATPase) complex, a key player in the acidification of internal compartments and a hub for metabolic signaling7,8, and of DCT-1/BNIP3, a mitochondrial protein involved in mitophagy and apoptosis9,10, accounts for the function of this miRNA in C. elegans. Surprisingly, although multiple V-ATPase subunits are upregulated in the absence of miR-1, this causes a loss-of-function of V-ATPase due to altered levels or stoichiometry, which negatively impact complex assembly. Finally, we demonstrate the conservation of the functional relationship between miR-1 and the V-ATPase complex in Drosophila.

cell biology↗