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

First Author  Robinton DA Year  2019
Journal  Dev Cell Volume  48
Issue  3 Pages  396-405.e3
PubMed ID  30661985 Mgi Jnum  J:272391
Mgi Id  MGI:6284029 Doi  10.1016/j.devcel.2018.12.016
Citation  Robinton DA, et al. (2019) The Lin28/let-7 Pathway Regulates the Mammalian Caudal Body Axis Elongation Program. Dev Cell 48(3):396-405.e3
abstractText  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.
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