Arturo Alvarez-Buylla, Ph.D.
My laboratory is interested in the mechanism and function of adult neurogenesis. We would like to understand neuronal birth, migration and differentiation in adult brains. In addition, we are interested in how new nerve cells are integrated and contribute to the function of adult brain circuits. On the last few years we have focused our work on the identification of the neural stem cells that function as the primary neuronal precursors in the adult brain. This led to a surprising conclusion.
We initially identified a region (SVZ) in the brain of adult mammals, close to the walls of the lateral ventricles, containing large numbers of neuronal precursors. Subsequently, we demonstrated that young neurons born in this brain region migrate a long distance through the anterior forebrain to complete their differentiation and become integrated in the olfactory bulb. This migration happens constantly and at a very high rate. Further work on this system led us to identify a novel form of neuronal translocation, called chain migration. This migration is unique in that young neurons move without the aid of radial glial or axonal guides. Instead, young neurons migrate closely associated to each other, forming long aggregates called chains. We have shown that there is a very extensive network of chains of young migrating neurons in the adult brain. Investigations into the origin of these new neurons lead us to the stem cells in the SVZ. Surprisingly, these cells correspond to astrocytes. Based on this finding we have suggested a new hypothesis that links early neuroepithelial cells, radial glia and stem cells as the stem cells of the development and adult brain. Work currently underway in the laboratory is trying to test this hypothesis. In addition we are working on the following related questions:
What is the mechanism of chain migration?
We would like to understand how neuronal precursors become organized into chains, how cells move in chains, what guides young neurons toward the olfactory bulb and where else in the adult and embryonic brain chain migration occurs.
What kinds of astrocytes can function as stem cells?
We are in search for better markers, in the embryo and in the adult, for neural stem cells. We are studying the molecular signals that regulate the proliferation and differentiation of neural stem cells.
What is the function of neurons formed in the adult brain and how do olfactory learning and olfactory discrimination affect neuronal recruitment in the olfactory bulb?
We are interested in behavioral or hormonal conditions that affect neuronal replacement in the olfactory bulb. In parallel we are developing techniques to stop neuronal production or migration to study their effects on the olfactory bulb and olfactory function.
Are neural stem cells in the postnatal brain the origin of brain tumors?
We are trying to test whether brain tumors originate from the astrocytes that function as stem cells in the adult brain.
Do human SVZ astrocytes have neural stem cells potential?
We have identified a band of stem cell astrocytes in the adult human brain. We are trying to determine the normal function of these cells.
The adult brain offers unique experimental advantages to study the mechanism of neuronal production, migration and differentiation: germinal layers contain fewer cells and are simpler in organization as compared to the embryo; neuronal production is not limited to a short window of time, but occurs over long periods; cell movements are not affected by major changes in brain structure; cells can be grafted into precise locations in the germinal layers. In addition, experimental manipulation of neuronal production, migration or survival in juveniles and adults will allow us to ask questions about the contribution of specific types of neurons to behavior and brain repair.