Biomedical subjects

Matías Hidalgo-Sánchez

Publications and source records attributed to Matías Hidalgo-Sánchez.

13 recordsLinked to original sources

PubMed2006

Developmental changes in the fibre population of the optic nerve follow an avian/mammalian-like pattern in the turtle Mauremys leprosa.

The changes in the axon and growth cone numbers in the optic nerve of the freshwater turtle Mauremys leprosa were studied by electron microscopy from the embryonic day 14 (E14) to E80, when the animals normally hatch, and from the first postnatal day (P0) to adulthood (5 years on). At E16, the first axons appeared in the optic nerve and were added slowly until E21. From E21, the fibre number increased rapidly, peaking at E34 (570,000 fibres). Thereafter, the axon number decreased sharply, and from E47 declined steadily until reaching the mature number (about 330,000). These observations indicated that during development of the retina there was an overproduction and later elimination of retinal ganglion cells. Growth cones were first observed in the optic nerve at as early as E16. Their number increased rapidly until E21 and continued to be high through E23 and E26. After E26, the number declined steeply and by E40 the optic nerve was devoid of growth cones. These results indicated that differentiation of the retinal ganglion cells occurred during the first half of the embryonic life. To examine the correlation between the loss of the fibres from the optic nerve and loss of the parent retinal ganglion cells, retinal sections were processed with the TUNEL technique. Apoptotic nuclei were detected in the ganglion cell layer throughout the period of loss of the optic fibres. Our results showed that the time course of the numbers of the fibres in the developing turtle optic nerve was similar to those found in birds and mammals.

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PubMed2006

Spatial and temporal patterns of proliferation and differentiation in the developing turtle eye.

Here we show for the first time different aspects of the pattern of neurogenesis in the developing turtle retina by using different morphological and molecular clues. We show the chronotopographical fashion of occurrence of three major aspects of retinal development: (1) morphogenesis of the optic primordia and emergence of the different retinal layers, (2) the temporal progression of neurogenesis by the cessation of proliferative activity, and (3) the apparition and cellular localization of different antigens and neuroactive substances. Retinal cells were generated in a conserved temporal order with ganglion cells born first, followed by amacrine, photoreceptor, horizontal and bipolar/Müller cells. While eventually expressed in many types of retinal neurons, Islet1 was permanently expressed in differentiating and mature ganglion cells. Calbindin-immunoreactive elements were found in the ganglion cell layer and the inner nuclear layer. Interestingly, at later stages the amount of expressing cells in these layers was reduced dramatically. On the contrary, the number of calbindin-immunoreactive photoreceptors increased as development proceeded. In addition, calretinin expressing cells were prominent in the horizontal cell bodies, and their processes extending into the outer plexiform layer were also strongly labeled. Finally, the synthesis of gamma-aminobutyric acid (GABA) was detected in developing and matured horizontal and amacrine cells. All these maturational features began in the dorso-central area, in a region slightly displaced towards the temporal retina.

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PubMed2006

Fgf19 expression patterns in the developing chick inner ear.

The inner ear is a complex sensorial structure with hearing and balance functions. A key aim of developmental biology is to understand the molecular and cellular mechanisms involved in the induction, patterning and innervation of the vertebrate inner ear. These developmental events could be mediated by the expression of regulating genes, such as the members of the family of Fibroblast Growth Factors (Fgfs). This work reports the detailed spatial and temporal patterns of Fgf19 expression in the developing inner ear from otic cup (stage 14) to 8 embryonic days (stage 34). In the earliest stages, Fgf19 and Fgf8 expressions determine two subdomains within the Fgf10-positive proneural-sensory territory. We show that, from the earliest stages, the Fgf19 expression was detected in the acoustic-vestibular ganglion and the macula utriculi. The Fgf19 gene was also strongly, but transiently, expressed in the macula lagena, whereas the macula neglecta never expressed this gene in the period analysed. The Fgf19 expression was also clearly observed in some borders of various sensory elements. These results could be useful from further investigations into the role of FGF19 in otic patterning.

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PubMed2005

A developmental profile of the levels of calcium pumps in chick cerebellum.

The functional expression and distribution of intracellular ATPase (sarco(endo)plasmic reticulum Ca(2+)-ATPase: SERCA) and plasma membrane Ca(2+)-ATPase (PMCA) was analyzed in the developing chick cerebellum. The activity and Ca(2+) uptake increase with development for both ATPases. However, the protein content increases with the stage of development only for SERCA, remaining constant for PMCA. Immunohistochemical assays showed that the ontogenesis of these ATPases goes along with definite stages of cerebellum histogenesis, and is complete at hatching. The SERCA is mainly distributed in Purkinje neurons, whereas the PMCA seems to be expressed initially in climbing fibers, shifting to soma and spiny branchlets of Purkinje cells at late embryonic stages. Granule cells express both ATPases according to their degree of maturity, whereas only PMCA is present in cerebellar glomeruli. These pumps are present in deep nuclei and the choroid plexus, although in this latter tissue their expression declines with development. The spatio-temporal distribution of SERCA and PMCA must be closely related to their association with the development of specific cells and processes of the chick cerebellum.

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PubMed2005

Expression of Fgf19 in the developing chick eye.

Fibroblast growth factor 19 (FGF19) is a new member of the FGF family of growth factors. Here, we describe the localization of Fgf19 mRNA in the developing chick retina and lens in stages from the Hamburger and Hamilton stage 15 (HH15) to postnatal day 30 (P30). Fgf19 was expressed in a transient manner in postmitotic neuroblasts during the migration from the ventricular surface to their final location. Moreover, from HH31 (embryonic day 7, E7) on, a subset of lined up Fgf19 expressing cells was distributed in the outer region of the presumptive INL. These cells were Pax6 immunoreactive horizontal cells. During the last third of embryogenesis, Fgf19 expression in the retina was progressively down-regulated and was not detected at P30. Also, it was transiently expressed in the equatorial region of the lens.

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PubMed2005

Specification of the meso-isthmo-cerebellar region: the Otx2/Gbx2 boundary.

The midbrain/hindbrain (MH) territory containing the mesencephalic and isthmocerebellar primordial is characterized by the expression of several families of regulatory genes including transcription factors (Otx, Gbx, En, and Pax) and signaling molecules (Fgf and Wnt). At earlier stages of avian neural tube, those genes present a dynamic expression pattern and only at HH18-20 onwards, when the mesencephalic/metencephalic constriction is coincident with the Otx2/Gbx2 boundary, their expression domains become more defined. This review summarizes experimental data concerning the genetic mechanisms involved in the specification of the midbrain/hindbrain territory emphasizing the chick/quail chimeric experiments leading to the discovery of a secondary isthmic organizer. Otx2 and Gbx2 co-regulation could determine the precise location of the MH boundary and involved in the inductive events characteristic of the isthmic organizer center.

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PubMed2005

A distinct preisthmic histogenetic domain is defined by overlap of Otx2 and Pax2 gene expression in the avian caudal midbrain.

Correlative in situ hybridization of Otx2, Pax2, Gbx2, and Fgf8 mRNA probes in adjacent serial sections through the chicken midbrain and isthmus at early to intermediate stages of development served to map in detail the area of overlap of Otx2 and Pax2 transcripts in the caudal midbrain. The neuronal populations developing within this preisthmic domain made up a caudal part of the midbrain reticular formation, the interfascicular nucleus, and the magnocellular (pre)isthmic nucleus, plus the corresponding part of the periaqueductal gray. The torus semicircularis-the inferior colliculus homolog-expressed Otx2 in its ventricular lining exclusively, but it never expressed Pax2. The parvicellular isthmic nucleus, although placed inside the midbrain lobe, never expressed Otx2, and its cells rapidly down-regulated an early transient Pax2 signal; this pattern is consistent with its reported isthmic origin and forward tangential translocation. This analysis reveals the existence of four distinct midbrain histogenetic domains along the longitudinal axis, at least for the alar plate. These presumably result from step-like isthmic organizer effects on Otx2-expressing midbrain neuroepithelium at different distances from a caudal FGF8 morphogen source (isthmic Fgf8-positive domain). The final phenotypes of these domains are histologically diverse and make up the griseum tectale (rostrally), the optic tectum, the torus semicircularis, and the presently characterized preisthmic domain (lying closest to the isthmic organizer). Available comparative data for reptiles and mammals suggest the general validity of this scheme.

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PubMed2005

Development of precerebellar nuclei: instructive factors and intracellular mediators in neuronal migration, survival and axon pathfinding.

The precerebellar system provides an interesting model to study tangential migrations. All precerebellar neurons (PCN) are generated in the most alar part of the hindbrain in a region called rhombic lip. PCN first emit a leading process and then translocate their nuclei inside it, a mechanism called nucleokinesis. In the past few years, molecular cues that could affect those processes have been investigated, with a special care on: (i) the identification of extrinsic factors directing cell migration and axon elongation as well as neuronal survival during development; (ii) intracellular reorganizations of the cytoskeleton during nucleokinesis in response to chemotropic factors. The signaling cascades, including regulators of actin and microtubule cytoskeleton, in response to diffusible guidance factors have raised an increasing attention. We will here review the role of guidance cues involved in PCN migration in particular netrin-1, Slit and Nr-CAM. We will also consider Rho-GTPases that have been proposed to mediate axon outgrowth and neuronal migration, especially in response to netrin-1, and which may act as a relay between extracellular signals and intracellular remodeling. Recent findings from in vitro pharmacological inhibition of various Rho-GTPases and over-expression of effectors bring molecular cues that, in accordance with anatomical data, fit the idea that nucleokinesis and axon outgrowth are not strictly coupled events during PCN migration.

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PubMed2005

Pax2 expression patterns in the developing chick inner ear.

The fate specification of the developing vertebrate inner ear could be determined by complex regulatory genetic pathways involving the Pax2/5/8 genes. Pax2 expression has been reported in the otic placode and vesicle of all vertebrates that have been studied. Loss-of-function experiments suggest that the Pax2 gene plays a key role in the development of the cochlear duct and acoustic ganglion. Despite all these data, the role of Pax2 gene in the specification of the otic epithelium is still only poorly defined. In the present work, we report a detailed study of the spatial and temporal Pax2 expression patterns during the development of the chick inner ear. In the period analysed, Pax2 is expressed only in some presumptive sensory patches, but not all, even though all sensory patches show the scattered Pax2 expression pattern later on. We also show that Pax2 is also expressed in several non-sensory structures.

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PubMed2004

Otx2, Gbx2, and Fgf8 expression patterns in the chick developing inner ear and their possible roles in otic specification and early innervation.

The chick inner ear is a complex structure containing auditory and vestibular sensory organs innervated by neurons of the acoustic-vestibular ganglion. The molecular signals involved in the specification and initial innervation of the otic epithelium are poorly understood. Here, we present a detailed description of the Otx2, Gbx2, and Fgf8 gene expression patterns in the chick developing inner ear, comparing them with the Bmp4 expression, a putative sensory-organ marker. The Otx2 expression was detected in the ventro-lateral wall of the otic anlage and could play a role in the segregation of the saccule and utricle maculae. The relationship between Gbx2 and Fgf8 expression changed during inner ear development but was always related to the macula sacculi innervation and endolymphatic duct formation. Our results also suggest that the maculae of the saccule and lagena, and the medial portion of the macula utriculi could arise within a broad Fgf8-positive domain previously observed at the otocyst stage. The spatial and temporal relationships between these gene expression domains and the initial innervation of the epithelium by some subpopulations of otic axons suggest that expression domain boundaries could be involved in the specification and early innervation of presumptive sensory patches.

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PubMed2004

Localization of endoplasmic reticulum and plasma membrane Ca2+-ATPases in subcellular fractions and sections of pig cerebellum.

Subcellular fractions and sections of the cerebellum were analysed to evaluate the relative activity and distribution of organellar and plasma membrane Ca2+-ATPases (SERCA and PMCA). Western blot analysis of the fractions with IID8 or Y/1F4 SERCA-specific antibodies or else with 5F10 or pbPMCA antibodies, specific to PMCA pump, revealed a major content of SERCA protein in microsomes and of PMCA protein in plasma membrane vesicles. The Ca2+-ATPase activity of microsomes was more sensitive to thapsigargin, a SERCA-specific inhibitor, whereas the activity of the plasma membrane vesicle fraction was inhibited more by vanadate, a blocker of PMCA activity. The SERCA and PMCA distribution analysed in cerebellar sections revealed IID8 antibody reactions in Purkinje cell cytoplasm, granule cells and cerebellar glomeruli. Y/1F4 gave immunostaining in Purkinje cells, molecular layer interneurons (basket and stellate cells) and glomeruli, but granule cells were not labelled. The 5F10 antibody reacted with Purkinje cells, including their dendritic spines, as well as cerebellar glomeruli, whereas the pbPMCA antibody labelled several processes in all three layers and some synaptic interaction sites. The differential content and localization of the two types of Ca2+ pumps in specific neuronal areas of pig cerebellum indicate precise Ca2+ requirements of specific cellular regions.

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PubMed2002

Temporal sequence of gene expression leading caudal prosencephalon to develop a midbrain/hindbrain phenotype.

Transplantation of prosomeres 1-2 into the cerebellar plate were used, by using chick/quail chimeras, to analyse the temporal sequence of the genetic cascade leading the graft to develop a midbrain/hindbrain phenotype. Our results show that (1) at Hamburger and Hamilton (HH) stage 13, Pax2 and En2 are already induced within the graft, before all other genes of the cascade, whereas misexpression of Fgf8 is also observed within the contiguous host cerebellar plate; (2) within the graft, Otx2 repression and Gbx2 induction (see Hidalgo-Sánchez et al. [1999] Development 126:3191-3203) are secondary events that affect, from stages HH14-15, the areas in contact with the host Gbx2/Fgf8-expressing cerebellar plate; (3) at these stages, the repressed Otx2 territory extends beyond the areas induced to express Gbx2, with the two territories not abutting before HH17-18; (4) Fgf8 expression becomes progressively induced within the Otx2-repressed/Gbx2-induced territory, starting at HH15-16. Our results support the hypothesis that the host-Gbx2/graft-Otx2 interface could trigger the genetic cascade induced within the graft and that the Gbx2-induced domain could play a key role during the establishment of the induced intragraft midbrain/hindbrain boundary.

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PubMedDate not supplied

Differential expression of Otx2, Gbx2, Pax2, and Fgf8 in the developing vestibular and auditory sensory organs.

The vertebrate inner ear is a complex organ with vestibular and auditory sensory functions, which derives from a single ectoderm structure, the otic placode. The development and regional patterning of the otic primordium is determined by the restricted expression of several genes. Here, we show the expression pattern of three transcription factors (Otx2, Gbx2, Pax2) and of a member of the fibroblast growth factor family (Fgf8) in the developing chick inner ear, and we correlate these patterns with the developing sensory and nonsensory elements.

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