Talk to the Veterans Crisis Line now
U.S. flag
An official website of the United States government
Veterans Benefits and Health Care About VA Find a VA Location

VA Health Systems Research

Go to the VA ORD website
Go to the QUERI website

HSR&D Citation Abstract

Search | Search by Center | Search by Source | Keywords in Title

MicroRNA governs bistable cell differentiation and lineage segregation via a noncanonical feedback.

Li CJ, Liau ES, Lee YH, Huang YZ, Liu Z, Willems A, Garside V, McGlinn E, Chen JA, Hong T. MicroRNA governs bistable cell differentiation and lineage segregation via a noncanonical feedback. Molecular systems biology. 2021 Apr 1; 17(4):e9945.

Dimensions for VA is a web-based tool available to VA staff that enables detailed searches of published research and research projects.

If you have VA-Intranet access, click here for more information vaww.hsrd.research.va.gov/dimensions/

VA staff not currently on the VA network can access Dimensions by registering for an account using their VA email address.    Search Dimensions for VA for this citation
* Don't have VA-internal network access or a VA email address? Try searching the free-to-the-public version of Dimensions


Abstract:

Positive feedback driven by transcriptional regulation has long been considered a key mechanism underlying cell lineage segregation during embryogenesis. Using the developing spinal cord as a paradigm, we found that canonical, transcription-driven feedback cannot explain robust lineage segregation of motor neuron subtypes marked by two cardinal factors, Hoxa5 and Hoxc8. We propose a feedback mechanism involving elementary microRNA-mRNA reaction circuits that differ from known feedback loop-like structures. Strikingly, we show that a wide range of biologically plausible post-transcriptional regulatory parameters are sufficient to generate bistable switches, a hallmark of positive feedback. Through mathematical analysis, we explain intuitively the hidden source of this feedback. Using embryonic stem cell differentiation and mouse genetics, we corroborate that microRNA-mRNA circuits govern tissue boundaries and hysteresis upon motor neuron differentiation with respect to transient morphogen signals. Our findings reveal a previously underappreciated feedback mechanism that may have widespread functions in cell fate decisions and tissue patterning.




Questions about the HSR website? Email the Web Team

Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.