PT  - JOURNAL ARTICLE
AU  - Rashid, Alina
AU  - Tevlin, Maya
AU  - Lu, Yun
AU  - Shaham, Shai
TI  - A developmental pathway for epithelial-to-motoneuron transformation in <em>C. elegans</em>
AID  - 10.1101/2022.05.27.493712
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.27.493712
4099  - http://biorxiv.org/content/early/2022/05/29/2022.05.27.493712.short
4100  - http://biorxiv.org/content/early/2022/05/29/2022.05.27.493712.full
AB  - Motoneurons and motoneuron-like pancreatic beta cells arise from radial glia and ductal cells, both tube-lining progenitors that share molecular regulators. To uncover programs underlying motoneuron formation, we studied a similar, cell-division-independent transformation of the C. elegans tube-lining Y cell into the PDA motoneuron. We find that lin-12/Notch acts through ngn-1/Ngn and its regulator hlh-16/Olig to control transformation timing. lin-12 loss blocks transformation, while lin-12(gf) promotes precocious PDA formation. Early basal expression of both ngn-1/Ngn and hlh-16/Olig depends on sem-4/Sall and egl-5/Hox. Later, coincident with Y-cell morphological changes, ngn-1/Ngn expression is upregulated in a sem-4/Sall and egl-5/Hox-dependent but hlh-16/Olig-independent manner. Subsequently, Y-cell retrograde extension forms an anchored process priming PDA axon extension. Extension requires ngn-1-dependent expression of the cytoskeleton organizers UNC-119, UNC-44/ANK, and UNC-33/CRMP, which also, unexpectedly, activate PDA terminal-gene expression. Our findings reveal key cell-division-independent regulatory events leading to motoneuron generation, suggesting a conserved pathway for epithelial-to-motoneuron/motoneuron-like differentiation.Competing Interest StatementThe authors have declared no competing interest.