A developmental pathway for epithelial-to-motoneuron transformation in C. elegans

Cell Rep. 2022 Sep 27;40(13):111414. doi: 10.1016/j.celrep.2022.111414.

Abstract

Motoneurons and motoneuron-like pancreatic β cells arise from radial glia and ductal cells, respectively, 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 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 activate PDA terminal-gene expression. Our findings uncover cell-division-independent regulatory events leading to motoneuron generation, suggesting a conserved pathway for epithelial-to-motoneuron/motoneuron-like cell differentiation.

Keywords: C. elegans; CP: Developmental biology; CP: Molecular biology; Notch; Y to PDA; ductal and islet cells; hlh-16; ngn-1; radial glia derived motoneurons; unc-119; unc-33; unc-44.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • Cell Differentiation
  • Motor Neurons / metabolism
  • Nerve Growth Factors / metabolism
  • Nerve Tissue Proteins / metabolism
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Transcription Factors
  • UNC-119 protein, C elegans
  • unc-33 protein, C elegans