Contact Information

Group leader

Maija Castrén, M.D., Ph.D.
+358-2941 25771
maija.castren (at) helsinki (dot) fi

Mailing address
Faculty of Medicine / Physiology
PO Box 63
00014 University of Helsinki
FINLAND

Street address
Haartmaninkatu 8
(Biomedicum Helsinki)
00290 Helsinki
FINLAND

Research

Aberrances in the regulation of the survival, proliferation, and differentiation of neural stem/progenitor cells (NPCs) are likely to be involved in the pathophysiology of several neurodevelopmental disorders. We have shown alterations in the differentiation and migration of mouse and human NPCs in fragile X syndrome (FXS) which provides us a model disorder to study molecular mechanisms underlying deficits in cognition, sensation, attention, and activity as well as autism which is seen in a subgroup of FXS individuals. The syndrome is caused by the absence of fragile X mental retardation protein (FMRP) which is an RNA binding protein that regulates the translation at the synaptic sites and is required for normal synaptic maturation and function.

NPCs can be cultured in cell clusters referred to as neurospheres in the presence of mitogens and the withdrawal of mitogens results in the differentiation of cells to different types of neuronal cells.


NPCs in neurospheres and cells differentiated from progenitors: neurons (red, TuJ1), astrocytes (blue, GFAP), and oligodendrocytes (green, O4).



From FXS NPCs differentiated neurons (red) migrating on glial cell (blue).
We have shown that FXS neural progenitors generate more cells that respond to metabotropic glutamate receptor activation and neurons with short neurite phenotype when compared with the differentiation of wild-type progenitors. The findings in vitro correlate with abnormalities in neuronal cell differentiation and metabotropic glutamate receptor signaling in vivo in Fmr1-knockout mice, the mouse model of FXS.