HOME ABOUT CONTACT AVAILABLE ISSUES SUBSCRIBE MEDIA & ADS
LATEST UPDATES » Vol 24, No. 09, September 2020 – 3D Technology: Additive Manufacturing Applications and Prospects       » Results of CD30 CAR-T Cell Therapy Trial Shows Promise for Hodgkin Lymphoma Patients       » Emerging Technologies and Innovations amid a Global Pandemic       » Monitoring COVID-19 Patients with AI-powered Platform       » Singapore Researchers Devise a Rapid COVID-19 Test Kit for the Detection of Neutralising Antibodies (NAbs) Against SARS-CoV-2       » Novel Ventilator Conceptualized by Singapore Clinicians Provides Efficient and Personalized Breathing Support for COVID-19 patients      
Vol 21, No. 05, May 2017   |   Issue PDF view/purchase
FEATURES
Spatiotemporal Control of Hox genes by microRNA
by Chung-Jung Li & Jun-An Chen
Institute of Molecular Biology, Academia Sinica

Hox genes have been extensively studied for more than 30 years. Although it is well-known that Hox genes are essential to the specification of spinal motor neuron subtype identities along the rostrocaudal axis, it remains unclear how the Hox genes are precisely regulated to achieve their collinear spatiotemporal expression. In collaboration with Prof. Qing Nie from the Mathematics Department of UC Irvine, Dr. Jun-An Chen from IMB Academia Sinica has uncovered a novel microRNA/Hox gene expression network that contributes to the dynamic control of Hox gene expression, thereby ensuring proper motor neuron subtype identities during development. This model was established by in silico mathematical simulations and was examined further using embryonic stem cell differentiation systems and investigations of mouse and chicken embryos. Their work was published in Nature Communications on 24 March 2017, under the title “MicroRNA Filters Hox Temporal Transcription Noise to Confer Boundary Formation in the Spinal Cord".

Hox genes are expressed in a specific spatial and temporal pattern during motor neuron development. These specific patterns then dictate the specification of particular subtypes of motor neurons, which in turn affects the innervation pattern of their respective muscle targets. Previous studies reported a delay in translation of Hox proteins from messenger RNA; whereas the messenger RNAs of Hox genes are detected at progenitor stages of motor neurons, Hox proteins are not translated until the later postmitotic stage.

MicroRNAs belong to a class of non-coding RNAs (ncRNAs) that regulate cell function by repressing the translation of target messenger RNAs after transcription. Dr. Chen and his collaborators hypothesized that microRNAs might mediate the delayed Hox protein translation. Indeed, when the microRNA-generating Dicer gene was deleted from motor neuron progenitor cells, they started to immediately translate Hoxa5 messenger RNA into proteins, i.e. before the postmitotic stage. The result of this early expression is a fuzzy distribution of Hoxa5 proteins that disrupts a particular Hox5-Hox8 boundary in postmitotic motor neurons. This boundary is essential for defining different motor neuron subtypes. The network of Hox genes and microRNAs were then explored in silico and two feed-forward Hox-microRNA loops were identified that accounted for the observed phenotypes. Finally, gain- and loss-of-function studies, both in vitro and in vivo, revealed a specific microRNA (mir-27) to be a major regulator of the temporal delay and spatial collinearity of Hox protein expression. It is notable that the mir-27-dependent phenotype established through the study of mice can be reproduced in chicken embryos, indicating that this novel Hox-microRNA genetic circuitry is essential and evolutionarily well-preserved.

This study was supported by Academia Sinica, MoST and NHRI.

Website:https://www.nature.com/articles/ncomms14685

Contact:
Dr. Jun-An Chen (Assistant research fellow, IMB, Academia Sinica)
jachen@imb.sinica.edu.tw
(Tel) +886-2-2788-0460
https://www.imb.sinica.edu.tw/~jachen/

NEWS CRUNCH  
news PharmaSources Launches the Export-Driven Event CPhI & P-MEC China E-Trade Season
news PharmaSources.com to Help Propel the Chinese API Export Business with E-Trade Session CPhI China Top API Exporters & Products
news Singapore Biomedical Company Appointed as a Certified Service Provider by 10x Genomics
news Proteona Honoured with "one to watch" Prize in the Inaugural Spinoff Prize by Nature Research and Merck Grou
SPOTLIGHT  

MAGAZINE TAGS
About Us
Events
Available issues
Editorial Board
Letters to Editor
Contribute to APBN
Advertise with Us
CONTACT
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
Tel: 65-6466-5775
Fax: 65-6467-7667
» For Editorial Enquiries:
   biotech_edit@wspc.com or Ms Deborah Seah
» For Subscriptions, Advertisements &
   Media Partnerships Enquiries:
   biotech_ad@wspc.com
Copyright© 2020 World Scientific Publishing Co Pte Ltd  •  Privacy Policy