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Research Departments > Molecular, Cellular and Developmental Neurobiology department > Molecular control of neurogenesis > Research Report

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Molecular control of neurogenesis

Our laboratory is interested in understanding the molecular basis behind the generation of new neurons both during the development of the nervous system and in the adult brain. The generation of new neurons is retained to some extent in niches in the adult nervous system throughout lifetime under physiological conditions and constitutes an important source of neural plasticity. However, adult neurogenesis is very restricted, both in number and subtypes of neural cells generated. Our lab is interested in exploring how differences in cell production rates and in the temporal extent of neurogenesis can be attained in the adult brain in comparison with developmental neurogenesis.

Over the years, we have contributed to understand what are the signals and the genetic programs that govern Neural Development. As for the signals, we have shown that FGF and retinoic acid are essential for the temporal control of the specification and migration of neural crest cells (Martínez-Morales, et al., 2011, Diez del Corral and Morales, 2014). Moreover, we have shown that FGF pathway modulates the activity of the Shh signalling pathway in ventral patterning of the spinal cord (Morales et al., 2016).

We have also contributed to establish how neurogenesis and cell fate specification during development is controlled through the modulation of signaling pathway such as Wnt canonical pathway. In that regard, the lab has also established that transcription factor Sox5 promotes cell cycle exit in neural progenitors and interneuron subtypes specification in the developing spinal cord, modulating Wnt canonical pathway (Martinez-Morales et al., 2010; Quiroga et al., 2015).

At present, we are studying how new neurons are generated from stem cells in the adult brain and when and how, during brain development, the adult neural stem cells were generated in certain specific areas of the brain such as the dentate gyrus (DG) of the hippocampus (Mira and Morales, 2019). In the adult DG, neural stem cells (NSCs) generate new granule cells throughout life. The majority of those NSCs are in a reversible state of quiescence, that protects the cells from DNA damage and the population from depletion. However, little is known, of how the acquisition of quiescence and the transition from quiescence to an active mitotic state is regulated. To understand this key process, our lab is exploring the consequences of the conditional lack of function of Sox5 and Sox6 in the mouse adult hippocampus and during the development of the dentate gyrus, using both in vivo and in vitro (neurospheres culture) approaches.

Moreover, we are also interested in the potential of adult neural stem cells as therapeutical tools in neurodegenerative diseases. We have recently discovered how some inhibitors of a protein involved in neurodegenerative diseases (LRRK2) can promote the generation of oligodendrocytes from adult brain neural stem cells (Zaldívar et al., 2020).

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