Heterochronic genes, such as lin-28 in C. elegans, act as developmental timing regulators, governing the succession of cell fates during development. Now, on p. 891, Eric Moss and co-workers reveal that vertebrate LIN28 has a similar function during neurogliogenesis in vitro. LIN28 is an RNA-binding protein that is expressed in many developing tissues and is downregulated as differentiation proceeds. It specifically binds to, and blocks, the processing of let-7 microRNA, the first heterochronic gene homolog discovered outside C. elegans. The researchers show that LIN28 expression is high in undifferentiated mouse embryonal carcinoma cells but is downregulated rapidly upon retinoic acid-induced differentiation. They show that constitutive LIN28 expression completely blocks gliogenesis and increases neurogenesis — normally, neurons differentiate first and then glial cells differentiate from some neurons. Different parts of LIN28 are responsible for this cell-fate increase and inhibition, the authors report. Moreover, LIN28 does not function exclusively by blocking let-7 microRNA. These data suggest that LIN28 might also function as a developmental timing regulator in vertebrates.

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2010