Dr. Luis Fernando Covarrubias Robles, on Sabbatical leave,

(covs<at>ibt.unam.mx)

► Click to visit my lab in Mexico.

Expanding mesencephalic dopaminergic precursors

The study of committed neural precursors has been hindered due to their transitory existence in large numbers and the difficulty to culture them without modifications of their specific intrinsic properties. Neural precursors expanded with growth factors lack the original identity (as determined by expression of specific markers) and induction to differentiate, for instance, into dopaminergic neurons, using a combination of extrinsic and intrinsic specific factors has failed. On the other hand, the induction of embryonic stem cells or ‘naïve’ neural precursors into dopaminergic neurons at high efficiency has not been achieved by simply giving some of the known factors required for specific differentiation. However, recently, high efficiency of dopaminergic differentiation of human embryonic stem cells was obtained by expressing an intrinsic determinant, Lmx1a, under the control of the promoter of the gene encoding nestin (a marker of neural precursors) and adding a combination of growth factors to the culture medium.

The mesencephalic dopaminergic neurons originate from a unique neurogenic niche, the floor plate, which in other regions is not neurogenic; thus, this may be an interesting population of neural precursors to study. In addition, patients suffering Parkinson Disease will benefit of having a convenient source of dopaminergic neurons for cell therapy. Although a lot efforts have been done to induce specific differentiation of a variety of stem cells, until now the success is limited. The collaboration with the Nagy Lab is focused in testing whether committed neural precursors (embryo- or ES cell-derived) can be amplified either by using an N-myc inducible system or by reprogramming neurons/neuronal progenitors into their immediate proliferating neural precursors. We are also considering the evaluation of the neural differentiation potential of reprogramming cells after transplantation to an embryonic neurogenic environment.