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Research Departments > Molecular, Cellular and Developmental Neurobiology department > Stem cells, neurogenesis and neurodegeneration > Research Report

Research Report Personnel Publications Other

Stem cells, neurogenesis and neurodegeneration

RESEARCH TOPICS

A general objective of our laboratory is to study how extracellular factors and transcription factors regulate the number of neural stem and progenitor cells. Likewise, we are also interested in how these molecules influence the formation of excitatory and inhibitory neurons. We are studying the functions and mechanisms of action of extracellular factors and transcription factors in these processes. A second objective of our research is the generation of dopaminergic neurons from fibroblasts isolated from Parkinsonian patients with the aims of using these neurons in cell transplantation and as cellular model of disease.

The research projects that are currently ongoing in the laboratory are focused on:


1) To study neurogenesis in the embryonic and adult olfactory bulb (OB). In particular:
- The role and mechanism of action of transcription factors Tbr1, Gsx2, Pax6, and Nurr1 in the olfactory bulb (OB), cerebral cortex, hippocampus, and subventricular zone.
- To investigate the neurogenic capacity of stem and progenitor cells in the adult OB in situ and in cell transplantation paradigms.

2) To study the role and action mechanisms of IGF-I and BDNF in the developing and adult brain:
- The role of IGF-I in neuronal migration and positioning as well as in synapse formation in the OB, the hippocampal dentate gyrus (DG), and SVZ.
- The role of BDNF in promoting synaptogenesis.

3) The generation of dopaminergic, cortical and hipocampal neurons from neural stem cells (NSCs) and from induced pluripotent stem cells (iPSCs) to develop cellular models of Parkinson´s disease and Alzheimer´s disease. Cell therapy. (In collaboration with Dr. Rosario Moratalla’s Laboratory, Cajal Institute).

The main scientific contributions resulting from these studies include:


1) The isolation of embryonic and adult OB cells with neural stem cell characteristics and the capacity to differentiate into mature neurons in culture and in vivo.

2) Our results indicate that the embryonic OB contains progenitor cells (expressing Dlx2 and Pax6) that differentiate into mature GABAergic and dopaminergic neurons in vivo.

3) The demonstration that IGF-I and PTEN regulate the proliferation and differentiation of the olfactory bulb stem cells by modulating P-AKT levels.

4) As a result of our studies, we have reached the conclusion that IGF-I may play an important role in the formation of the neuronal layers within the OB and in neuroblast migration from the SVZ to the OB.

5) The expression of the transcription factor T-box brain 1 (Tbr1) in neural progenitors appears to regulate the generation of neurons and glial cells.

Methodology

  • Cell culture of embryonic and adult neural stem cells
  • Neuronal cultures
  • Slice cultures
  • Transgenic and knockout mice
  • Cell transplantation in the embryonic, postnatal and adult brain
  • Gain-of-function and loss-of-function techniques to overexpress and knockdown, respectively, transcription factors in neural stem and progenitor cells
  • Cell culture of induced pluripotent stem cells (iPSCs) isolated from human fibroblasts followed by differentiation iPSCs into dopaminergic neurons and other neuronal subtypes.
Imagen Carlos Vicario

 


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