miR-335 promotes mesendodermal lineage segregation and shapes a transcription factor gradient in the endoderm
Yang D, Lutter D, Burtscher I, Uetzmann L, Theis FJ, Lickert H (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Book Volume: 141
Pages Range: 514-525
Journal Issue: 3
DOI: 10.1242/dev.104232
Abstract
Transcription factors (TFs) pattern developing tissues and determine cell fates; however, how spatio-temporal TF gradients are generated is ill defined. Here we show that miR-335 fine-tunes TF gradients in the endoderm and promotes mesendodermal lineage segregation. Initially, we identified miR-335 as a regulated intronic miRNA in differentiating embryonic stem cells (ESCs). miR-335 is encoded in the mesoderm-specific transcript (Mest) and targets the 3′-UTRs of the endoderm-determining TFs Foxa2 and Sox17. Mest and miR-335 are co-expressed and highly accumulate in the mesoderm, but are transiently expressed in endoderm progenitors. Overexpression of miR-335 does not affect initial mesendoderm induction, but blocks Foxa2- and Sox17-mediated endoderm differentiation in ESCs and ESC-derived embryos. Conversely, inhibition of miR-335 activity leads to increased Foxa2 and Sox17 protein accumulation and endoderm formation. Mathematical modeling predicts that transient miR-335 expression in endoderm progenitors shapes a TF gradient in the endoderm, which we confirm by functional studies in vivo. Taken together, our results suggest that miR-335 targets endoderm TFs for spatio-temporal gradient formation in the endoderm and to stabilize lineage decisions during mesendoderm formation. © 2014.
Involved external institutions
Germany (DE)How to cite
APA:
Yang, D., Lutter, D., Burtscher, I., Uetzmann, L., Theis, F.J., & Lickert, H. (2014). miR-335 promotes mesendodermal lineage segregation and shapes a transcription factor gradient in the endoderm. Development, 141(3), 514-525. https://doi.org/10.1242/dev.104232
MLA:
Yang, Dapeng, et al. "miR-335 promotes mesendodermal lineage segregation and shapes a transcription factor gradient in the endoderm." Development 141.3 (2014): 514-525.
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