Fetal brain development, stem cells, microRNAs and teratology
Fetal brain development: During the second and third trimester, the fetal brain grows at an enormous rate to generate the billions of neurons and glial cells of the brain and spinal cord. A thin layer of neural stem cells in the walls of the brain’s ventricles supports this enormous growth requirement. Our laboratory is interested in understanding the biological steps that transform uncommitted stem cells into neurons or a glial cells. To address this question, our laboratory has begun to focus on understanding the roles of a non-protein coding RNA molecules, in particular microRNAs.
MicroRNAs. The world of non-coding RNA (Ribonucleic acid) molecules represents a paradigm shift in biology, away from the central dogma of biology which places RNA molecules as mere messengers between DNA and protein synthesis. However, more than 90% of the RNA molecules made by a cell are not destined to be translated into proteins. Instead, these evolutionary ancient molecules can do many things that proteins themselves can do, i.e., act as enzymes, signaling molecules and transcription factors for example. MicroRNAs are small non-coding RNAs, whose function is to regulate the expression of large networks of genes, to shape cell fate. Our laboratory is very interested in identifying key microRNAs that control the transformation of stem cells into neurons. These types of microRNAs will be important candidate molecules in the emerging arena of RNA therapies.
Teratology. The maternal-fetal environment is complex, and can include a variety of toxic agents that can damage the fetus. Alcohol is a particularly damaging agent for the fetus, and maternal alcohol consumption during pregnancy is the leading cause of mental retardation and birth defects in the Unites States. Our laboratory works on the hypothesis that the process of stem cell transformation opens up a window of vulnerability to the external environment, and to drugs of abuse, like alcohol. We have found that alcohol promotes stem cell maturation, and consequent depletion. This alcohol sensitivity is mediated by a small group of microRNAs like miR335, miR153, miR21 and miR9. We are currently investigating what role these ‘teratogen-sensitive microRNAs’ play in fetal brain growth, and the spatial patterning of the emerging forebrain. We hypothesize that these types of microRNAs will play a key role in recruiting residual stem cells in both the developing and adult brain to stimulate the brain’s intrinsic regenerative capacity.