Estela Carnicero - Academia.edu (original) (raw)

Papers by Estela Carnicero

Audiology and Neuro-Otology, 2002

One of the more intriguing subjects in neuroscience is how a precursor or stem cell is induced to... more One of the more intriguing subjects in neuroscience is how a precursor or stem cell is induced to differentiate into a neuron. Neurogenesis begins early in brain development and suddenly becomes a very intense process, which is related with the influence of Retinoic Acid. Here, using a biological test (F9-1.8 cells) in chick embryos, we show that-in vivo‖ embryonic cerebrospinal fluid regulates mesencephalic-rombencephalic Isthmic Retinoic Acid synthesis and this effect has a direct influence on mesencephalic neuroepithelial precursors, inducing a significant increase in neurogenesis. This effect is mediated by the Retinol Binding Protein present in the embryonic cerebrospinal fluid. The knowledge of embryonic neurogenetic stimulus could be useful in the control of adult brain neurogenesis.

Development, 2000

Loss-of-function experiments in avians and mammals have provided conflicting results on the capac... more Loss-of-function experiments in avians and mammals have provided conflicting results on the capacity of fibroblast growth factor 3 (FGF3) to act as a secreted growth factor responsible for induction and morphogenesis of the vertebrate inner ear. Using a novel technique for gene transfer into chicken embryos, we have readdressed the role of FGF3 during inner ear development in avians. We find that ectopic expression of FGF3 results in the formation of ectopic placodes which express otic marker genes. The ectopically induced placodes form vesicles which show the characteristic gene expression pattern of a developing inner ear. Ectopic expression of FGF3 also influences the formation of the normal orthotopic inner ear, whereas another member of the FGF family, FGF2, shows no effects on inner ear induction. These results demonstrate that a single gene can induce inner ear fate and reveal an unexpectedly widespread competence of the surface ectoderm to form sensory placodes in higher ver...

Developmental Dynamics, 2019

BackgroundAt the earliest stages of brain development, the neuroepithelium works as an interdepen... more BackgroundAt the earliest stages of brain development, the neuroepithelium works as an interdependent functional entity together with cerebrospinal fluid, which plays a key regulatory role in neuroepithelial cell survival, replication and neurogenesis; however, the underlying mechanism remains unknown in mammals.ResultsWe show the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), in 13.5‐day rat embryo cerebrospinal fluid (eCSF). Immunohistochemical detection of FGF2 expression localized this factor inside neuroepithelial precursors close to the neuroepithelial‐CSF interface, suggesting that FGF2 from eCSF could originate in the neuroepithelium by apical secretion. The colocalization of FGFR1 and FGF2 in some neuroepithelial cells close to the ventricular surface suggests they are target cells for eCSF FGF2. Brain neuroepithelium EGF expression was negative. By using a neuroepithelial organotypic culture, we demonstrate that FGF2 and EGF from eCSF play...

Frontiers in neuroanatomy, 2017

Neurogenesis is a very intensive process during early embryonic brain development, becoming drama... more Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that i...

Journal of Cell Biology, 1999

The presence and physiological role of Ca 2 ϩinduced Ca 2 ϩ release (CICR) in nonmuscle excitable... more The presence and physiological role of Ca 2 ϩinduced Ca 2 ϩ release (CICR) in nonmuscle excitable cells has been investigated only indirectly through measurements of cytosolic [Ca 2 ϩ ] ([Ca 2 ϩ ] c). Using targeted aequorin, we have directly monitored [Ca 2 ϩ ] changes inside the ER ([Ca 2 ϩ ] ER) in bovine adrenal chromaffin cells. Ca 2 ϩ entry induced by cell depolarization triggered a transient Ca 2 ϩ release from the ER that was highly dependent on [Ca 2 ϩ ] ER and sensitized by low concentrations of caffeine. Caffeine-induced Ca 2 ϩ release was quantal in nature due to modulation by [Ca 2 ϩ ] ER. Whereas caffeine released essentially all the Ca 2 ϩ from the ER, inositol 1,4,5-trisphosphate (InsP 3)producing agonists released only 60-80%. Both InsP 3 and caffeine emptied completely the ER in digitonin-permeabilized cells whereas cyclic ADP-ribose had no effect. Ryanodine induced permanent emptying of the Ca 2 ϩ stores in a use-dependent manner after activation by caffeine. Fast confocal [Ca 2 ϩ ] c measurements showed that the wave of [Ca 2 ϩ ] c induced by 100-ms depolarizing pulses in voltage-clamped cells was delayed and reduced in intensity in ryanodine-treated cells. Our results indicate that the ER of chromaffin cells behaves mostly as a single homogeneous thapsigargin-sensitive Ca 2 ϩ pool that can release Ca 2 ϩ both via InsP 3 receptors or CICR.

Croatian Medical Journal, 2014

Due to the effort of several research teams across the world, today we have a solid base of knowl... more Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called “embryonic CSF.” Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life.

Journal of Developmental Biology, 2014

Regenerative Medicine, 2012

Aim: Hearing loss is the most common sensory disorder in humans, its main cause being the loss of... more Aim: Hearing loss is the most common sensory disorder in humans, its main cause being the loss of cochlear hair cells. We studied the potential of human mesenchymal stem cells (hMSCs) to differentiate towards hair cells and auditory neurons. Materials & methods: hMSCs were first differentiated to neural progenitors and subsequently to hair cell- or auditory neuron-like cells using in vitro culture methods. Results: Differentiation of hMSCs to an intermediate neural progenitor stage was critical for obtaining inner ear sensory lineages. hMSCs generated hair cell-like cells only when neural progenitors derived from nonadherent hMSC cultures grown in serum-free medium were exposed to EGF and retinoic acid. Auditory neuron-like cells were obtained when treated with retinoic acid, and in the presence of defined growth factor combinations containing Sonic Hedgehog. Conclusion: The results show the potential of hMSCs to give rise to inner ear sensory cells.

Neuroscience Letters, 2002

Neurotrophin-3 (NT-3) is one of the most potent stimulators for survival of auditory sensory neur... more Neurotrophin-3 (NT-3) is one of the most potent stimulators for survival of auditory sensory neurons. Viral transfer of neurotrophins into auditory neurons may offer a route to provide a permanent supply of the growth factor and guarantee their long-term survival. Herpes simplex virus type 1 (HSV-1)-based vectors have demonstrated their effectiveness to transfer genes into peripheral sensory neurons. In the present report, we have produced a HSV-1-based amplicon vector expressing NT-3. This vector efficiently infects isolated auditory neurons and stimulates their survival during distinct developmental stages of the inner ear. Therefore, this vector may present a unique entry point to develop therapies preventing or treating hearing impairment caused by the degeneration of auditory neurons.

Nature Cell Biology, 1999

Journal of Neurovirology, 1999

Journal of Neuroscience Research, 2004

Journal of Neurochemistry, 2001

The importance of individual members of the fibroblast growth factor gene family during innervati... more The importance of individual members of the fibroblast growth factor gene family during innervation of the vertebrate inner ear is not clearly defined. Here we address the role of fibroblast growth factor 2 (FGF‐2 or basic FGF) during development of the chicken inner ear. We found that FGF‐2 stimulated survival of isolated cochlear and vestibular neurons during distinct phases of inner ear innervation. The potential neurotrophic role of FGF‐2 was confirmed by its expression in the corresponding sensory epithelia and the detection of one of its high‐affinity receptors in inner ear neurons. Finally, we have analysed the potential of the amplicon system based on defective herpes simplex virus type 1 (HSV‐1) vectors to express FGF‐2 in cochlear neurons. Overexpression of FGF‐2 in cochlear neurons resulted in neuronal differentiation demonstrating the presence of biologically active growth factor. This study underlines the potential of FGF‐2 to control innervation and development of sens...

Journal of Neurochemistry, 2002

Developmental Dynamics, 2011

Embryonic‐cerebrospinal fluid (E‐CSF) plays crucial roles in early brain development including th... more Embryonic‐cerebrospinal fluid (E‐CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E‐CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E‐CSF contains all‐trans‐retinol and retinol‐binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic‐rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E‐CSF helps to control RA synthesis in the IsO by means of the RBP and all‐trans‐retinol it contains; (2) E‐CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E‐CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. Developmental...

Developmental Biology, 2006

Cells Tissues Organs, 2013

Introduction: There is a nondeveloped neurogenic potential in the adult mammalian brain, which co... more Introduction: There is a nondeveloped neurogenic potential in the adult mammalian brain, which could be the basis for neuroregenerative strategies. Many research efforts have been made to understand the control mechanisms which regulate the transition from a neural precursor to a neuron in the adult brain. Embryonic cerebrospinal fluid (CSF) is a complex fluid which has been shown to play a key role in neural precursor behavior during development, working as a powerful neurogenic inductor. We tested if the neurogenic properties of embryonic CSF are able to increase the neurogenic activity of neuronal precursors from the subventricular zone (SVZ) in the brains of adult mice. Results: Our results show that mouse embryonic CSF significantly increases the neurogenic activity in precursor cells from adult brain SVZ. This intense neurogenic effect was specific for embryonic CSF and was not induced by adult CSF. Conclusions: Embryonic CSF is a powerful neurogenesis inductor in homologous n...

Cells Tissues Organs, 2008

Previous studies have demonstrated that during neural fold fusion in different species, an apical... more Previous studies have demonstrated that during neural fold fusion in different species, an apical extracellular material rich in glycoconjugates is involved. However, the composition and the biological role of this material remain undetermined. In this paper, we show that this extracellular matrix in rat increases notably prior to contact between the neural folds, suggesting the dynamic behaviour of the secretory process. Immunostaining has allowed us to demonstrate that this extracellular matrix contains chondroitin sulphate proteoglycan (CSPG), with a spatio-temporal distribution pattern, suggesting a direct relationship with the process of adhesion. The degree of CSPG involvement in cephalic neural fold fusion in rat embryos was determined by treatment with specific glycosidases.In vitro rat embryo culture and microinjection techniques were employed to carry out selective digestion, with chondroitinase AC, of the CSPG on the apical surface of the neural folds; this was done immed...