Regulation of progenitor cell fate determines the numbers of neurons in the developing brain. While proliferation of neural progenitors predominates during early central nervous system (CNS) development, progenitor cell fate shifts toward differentiation as CNS circuits develop, suggesting that signals from developing circuits may regulate proliferation and differentiation. We tested whether activity regulates neurogenesis in vivo in the developing visual system of Xenopus tadpoles. Both cell proliferation and the number of musashi1-immunoreactive progenitors in the optic tectum decrease as visual system connections become stronger. Visual deprivation for 2 days increased proliferation of musashi1-immunoreactive radial glial progenitors, while visual experience increased neuronal differentiation. Morpholino-mediated knockdown and overexpression of musashi1 indicate that musashi1 is necessary and sufficient for neural progenitor proliferation in the CNS. These data demonstrate a mechanism by which increased brain activity in developing circuits decreases cell proliferation and increases neuronal differentiation through the downregulation of musashi1 in response to circuit activity.
PubMed ID: 21040846
PMC ID: PMC3005332
Article link: Neuron.
Grant support: DP10D000458 NCCDPHP CDC HHS, DP1 OD000458-02 NCCDPHP CDC HHS, DP1 OD000458-03 NCCDPHP CDC HHS, DP1 OD000458-04 NCCDPHP CDC HHS, DP1 OD000458-05 NCCDPHP CDC HHS, DP1 OD000458-02 NIH HHS , DP1 OD000458-03 NIH HHS , DP1 OD000458-04 NIH HHS , DP1 OD000458-05 NIH HHS , DP1 OD000458 NIH HHS
Genes referenced: msi1
Morpholinos referenced: msi1 MO1