During embryonic development of the nervous system, neural stem cells (NSCs) are responsible for generating the different types of neurons and glial cells in each of its different regions. The control of the correct proliferative and differentiative activity of these NSCs is crucial to form the complex network of connections that will allow the brain to function properly throughout an individual's life. Although neurogenesis was long considered to be exclusive to embryonic periods, it persists in a restricted manner after birth in specialised microenvironments or niches. Despite the incessant production of new neurons, adult NSCs are relatively quiescent and show high cell cycle control. Neurogenic niches appear to dynamically regulate NSC activity both in homeostasis and in situations of injury, through extrinsic signals (niche signals) that modulate the quiescence-activation state of NSCs, their self-renewal and the production of progeny.
Our group is therefore interested in
- The molecular mechanisms that regulate the proliferation and differentiation of NSCs both during development and in the adult stage.
- The molecular regulation of the quiescent state and
- its relationship with elements of the natural microenvironment or niche that these cells occupy.
Disturbances in the production of the correct number of different neuronal types are associated with various neurodevelopmental disorders, such as autism, schizophrenia or mental retardation. Likewise, changes in neurogenic niches that occur with ageing and disease, including neurodegenerative diseases such as Parkinson's, can profoundly affect the function of NSCs. On the other hand, loss of regulation in the behaviour of these cells can induce pathologies such as cancer. Thus, the study of these regulatory mechanisms has implications not only for our understanding of the basic biology of these cell populations but also for aspects related to pathology and loss of homeostasis.
With respect to the study of neurodevelopmental alterations, our group analyses how defects in the proliferation of NSCs during the development of the cerebral cortex are related to cognitive and social alterations such as those observed in patients with autism spectrum disorders. To this end, we have murine models that affect adhesion molecules and show macrocephaly as observed in a subpopulation of autistic individuals.
In relation to neurodegenerative processes, the group performs genetic-functional analysis of molecules in which mutations have been mapped that are associated with familial cases of Parkinson's disease, such as alpha-synuclein. We studied the possible normal function of these molecules and their relationship with neurodegeneration using genetically modified mouse strains (transgenic, null mutants...) or infection with viral vectors for somatic modification.
For NSCs, we have characterised intracellular signalling signals and pathways involved in the control of their activation/quiescence, their genetic stability and the maintenance of their potentiality, derived from the interaction of these cells with vascular elements, innervation or cells that inhabit with them in the neurogenic niches both embryonically, postnatally and in the adult state.
We have also studied some intrinsic regulators, especially those that regulate the cell cycle of NSCs or their response to damage. Finally, we are studying epigenetic mechanisms, such as genomic imprinting, that regulate the function of NSCs and the process of adult neurogenesis. Apart from the specific studies within each of these lines, we work on aspects that combine all of them and that have to do with the regulation of embryonic and adult neurogenesis in physiological and pathological conditions.
- Study of the cellular basis of Parkinson's disease.
- Study of innervation as an element of neurogenic niches.
- Study of the molecular basis of the quiescent state of NSCs.
- Study of inflammation as an element of the interaction between the neurogenic niche and the systemic environment.
- Role of genomic imprinting and its epigenetic regulation in neural stem cells: relationship to brain tumour formation.
- Study of the molecular mechanisms that control the balance between proliferation and differentiation of cortical NSCs and their relationship with neurodevelopmental diseases.
- Study of factors regulating the quiescence state of NSCs
Study of the molecular mechanisms responsible for the maintenance and correct functioning of NSCs in the adult brain. Specifically, we aim to address the study of how quiescence is regulated at the molecular level and how quiescence-activation responds to niche elements.
- Role of genomic imprinting and its epigenetic regulation in neural stem cells
This line aims to study basic epigenetic regulation (focusing on genomic imprinting) in NSCs under physiological conditions, and to identify novel epigenetic mechanisms that can potentially be modulated during reactivation therapies or tumour formation.
- Regulation of NSCs during the development of the cerebral cortex and their relation to neurodevelopmental diseases
In this line of work we aim to study the cellular and molecular mechanisms that regulate the correct balance between the production and specification of cerebral cortex cells by NSCs. We also aim to understand how alterations in these processes are related to neurodevelopmental diseases such as autism by studying murine models of these disorders.
- Study of the cellular basis of Parkinson's disease
Study of the alterations associated with or causing the degeneration of dopaminergic neurons and their relationship with ageing and associated conditioning factors. Studies of the effects of Parkinsonism on the behaviour of NSCs.
- FARIÑA GOMEZ, MARIA ISABEL
- PDI-Catedratic/a d'Universitat
- CWETSCH -, ANDRZEJ
- PI-Invest Disting Exper.Internacional
- DUART ABADIA, PERE
- Alumn.-Servei de Formacio Permanent
- GIL SANZ, CRISTINA
- Alumn.-Servei de Formacio Permanent
- KIRSTEIN, MARTINA
- PDI-Titular d'Universitat
- LOPEZ FABUEL, IRENE
- Alumn.-Servei de Formacio Permanent
- PEREZ SANCHEZ, FRANCISCO
- PDI-Titular d'Universitat
- Vicedega/Vicedegana / Vicedirector/a Ets
- RODRIGUEZ FERRON, SACRAMENTO
- PDI-Titular d'Universitat
- SIREROL PIQUER, MARIA SALOME
- Alumn.-Servei de Formacio Permanent
- Coordinador/a de Mobilitat
- FABRA BESER, JAIME
- Doctorand.
- JIMENEZ VILLALBA, ESTEBAN
- Doctorand.
- LAZARO CAROT, LAURA
- Doctorand.
Work team:
- Jordan Pla, Antonio - Consejo Superior de Investigaciones Científicas - Instituto de Biomedicina de Valencia
- ExpandirFARIÑA GOMEZ, MARIA ISABELPDI-Catedratic/a d'Universitat
- ExpandirKIRSTEIN, MARTINAPDI-Titular d'Universitat
- ExpandirPEREZ SANCHEZ, FRANCISCOPDI-Titular d'UniversitatVicedega/Vicedegana / Vicedirector/a Ets
- ExpandirRODRIGUEZ FERRON, SACRAMENTOPDI-Titular d'Universitat
- ExpandirCWETSCH -, ANDRZEJPI-Invest Disting Exper.Internacional
Burjassot/Paterna Campus
C/ Dr. Moliner, 50
46100 Burjassot (Valencia)
- FARIÑA GOMEZ, MARIA ISABEL
- PDI-Catedratic/a d'Universitat
