GIUV2017-370
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...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.
[Read more][Hide]
[Read more][Hide]
- Estudio de las bases celulares de la enfermedad de parkinson
- Estudio de la inervacion como elemento de los nichos neurogenicos.
- Estudio de las bases moleculares del estado de quiescencia de las NSCs.
- Estudio de la inflamacion como elemento de la interaccion entre nicho neurogenico y medio sistemico.
- Papel de la impronta genomica y su regulacion epigenetica en celulas madre neurales: relacion con la formacion de tumores cerebrales
- Estudio de los mecanismos moleculares que controlan el balance entre proliferacion y diferenciacion de las NSCs corticales y su relacion con las enfermedades del neurodesarrollo.
- 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 neural stem cells (NSCs).
- Study of factors regulating the quiescence state of NSCs.Study of the molecular mechanisms responsible for the maintenance and correct functioning of neural stem cells (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 neural stem cells (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 neural stem cells (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.
| Name | Nature of participation | Entity | Description |
|---|---|---|---|
| MARIA ISABEL FARIÑA GOMEZ | Director | Universitat de València | |
| Research team | |||
| FRANCISCO PEREZ SANCHEZ | Member | Universitat de València | |
| SACRAMENTO RODRIGUEZ FERRON | Member | Universitat de València | |
| ISABEL MARTINEZ GARAY | Member | Universitat de València | |
| MARTINA KIRSTEIN | Member | Universitat de València | |
| CRISTINA GIL SANZ | Member | Universitat de València | |
| GERMAN BELENGUER SANCHEZ | Member | Universitat de València | |
| PAU CARRILLO BARBERA | Member | Universitat de València | |
| JOSE MANUEL MORANTE REDOLAT | Member | Universitat de València | |
| IRENE LOPEZ FABUEL | Member | Universitat de València | |
| ANDRZEJ CWETSCH | Member | Universitat de València | |
| AZUCENA PEREZ CAÑAMAS | Member | Universitat de València | |
| CHIARA SGATTONI | Member | Universitat de València | |
| ALBA MARIN GARNES | Member | Universitat de València | |
| SARA ROJAS VAZQUEZ | Member | Universitat de València | |
| JAIME FABRA BESER | Collaborator | Universitat de València | |
| MARTA IGUAL LOPEZ | Collaborator | Universitat de València | |
| CARMEN MARIA MATEOS MARTINEZ | Collaborator | Universitat de València | |
| JENNIFER DIAZ MONCHO | Collaborator | Universitat de València | |
| DANIEL SAMPER LLAVADOR | Collaborator | Universitat de València | |
| TOMAS VIUDA MORENO | Collaborator | Universitat de València | |
- ERI Biotechnology and Biomedicine (BIOTECMED)
- Parkinson, Sinucleina, Inervación, Neurodegeneración
- Célula madre neural, NSC, quiescencia, activación,neurogénesis, reparación cerebral.
- Impronta Genómica, NSC, expresión génica, metilación, tumores
- Corteza Cerebral, NSC, Proliferación, DIferenciación, Enfermedades del Neurodesarrollo
