The Lin28/let-7 Pathway Regulates the Mammalian Caudal Body Axis Elongation Program

Dev Cell. 2019 Feb 11;48(3):396-405.e3. doi: 10.1016/j.devcel.2018.12.016. Epub 2019 Jan 17.


The heterochronic genes Lin28a/b and let-7 regulate invertebrate development, but their functions in patterning the mammalian body plan remain unexplored. Here, we describe how Lin28/let-7 influence caudal vertebrae number during body axis formation. We found that FoxD1-driven overexpression of Lin28a strikingly increased caudal vertebrae number and tail bud cell proliferation, whereas its knockout did the opposite. Lin28a overexpression downregulated the neural marker Sox2, causing a pro-mesodermal phenotype with a decreased proportion of neural tissue relative to nascent mesoderm. Manipulating Lin28a and let-7 led to opposite effects, and manipulating Lin28a's paralog, LIN28B caused similar yet distinct phenotypes. These findings suggest that Lin28/let-7 play a role in the regulation of tail length through heterochrony of the body plan. We propose that the Lin28/let-7 pathway controls the pool of caudal progenitors during tail development, promoting their self-renewal and balancing neural versus mesodermal cell fate decisions.

Keywords: Lin28; Sox2; body axis elongation; body plan; cell fate; development; heterochrony; let-7 miRNA; somitogenesis; tail bud.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Mammals / metabolism
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Morphogenesis / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*


  • Lin-28 protein, mouse
  • MicroRNAs
  • RNA-Binding Proteins
  • mirnlet7 microRNA, mouse