Non-coding RNAs in human disease

Molecular and Cellular Neurobiology
Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM (IIBM)

Role of microRNAs in neurogenesis and neuronal reprogramming

Neurogenesis is the process by which neural progenitor cells differentiate into mature neurons. This occurs during embryonic development in certain regions of the adult brain. In addition, recent studies suggest that glial cells of lesioned areas of the brain and spinal cord can be converted directly into neurons through the expression of neurogenic factors. This strategy, known as direct neuronal reprogramming, represents a promising alternative in regenerative medicine of the nervous system. Both natural neurogenesis and that induced by reprogramming require the correct integration of the new neurons which involves the formation of axons and dendrites to connect with different brain regions, often far away from the cell soma. Thus, controlling the growth of these neuronal prolongations is of great interest but the molecular mechanisms that regulate the growth and guidance of neurites remain poorly understood. In the laboratory we are interested in studying the role of microRNAs (miRNAs) in health and disease, and to develop new miRNA-based therapeutic strategies.  MiRNAs are 19–23 nucleotides long endogenously encoded small RNAs that regulate a wide variety of cellular processes by pairing through imperfect sequence complementarity with its target messenger RNAs and promoting mRNA degradation and/or translational repression. Our preliminary data indicated that miR-148a expression in adult brain is localized in regions characterized by the presence of neurons with axons of long projection. In addition, this miRNA induced the formation of axons and the reduction of dendrites in reprogrammed neurons from mouse postnatal cortical astrocytes suggesting that miR-148a plays a critical role in neuritogenesis. The present project will focus on studying the role of miR-148a in the development of neurites and axons of neurons obtained from neural progenitors and those obtained from postnatal reprogrammed astrocytes.

Biomolecules & Cell D.
Molecular Biomedicine
Alicia González Martín