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Salvador Martinez – 1st expert on this subject based on the ideXlab platform
Expression of chick Fgf19 and mouse Fgf15 orthologs is regulated in the developing brain by Fgf8 and ShhDevelopmental Dynamics, 2020Co-Authors: Leticia Gimeno, Salvador MartinezAbstract:
Fibroblast growth factors (Fgfs) constitute a family of signaling molecules that play essential roles in development. We have studied the expression pattern of mouse Fgf15 in the developing brain. Fgf19 is another member of the FGF family that has been suggested as the chick and human ortholog of mouse and rat Fgf15. Here, we compare the expression pattern during neural development of chick Fgf19 with mouse Fgf15. Unlike Fgf15, Fgf19 presents an expression in the isthmic Alar Plate, diencephalic and mesencephalic parabasal Plates, hindbrain basal Plate, as well as in the zona limitans intrathalamica (zli). Moreover, we explored the regulation between Fgf19 and the signaling molecules of the isthmic and zli organizers: Fgf8 and Shh, respectively. Considering the possibility that Fgf19 plays a similar role in humans and chicks, this finding could explain the significant diencephalic phenotypic differences between humans and mice in models and diseases where the Shh pathway is affected.
Fgf15 regulates thalamic development by controlling the expression of proneural genesBrain Structure and Function, 2016Co-Authors: Almudena Martinez-ferre, John L R Rubenstein, Cosme Lloret-quesada, Nilima Prakash, Wolfgang Wurst, Salvador MartinezAbstract:
The establishment of the brain structural complexity requires a precisely orchestrated interplay between extrinsic and intrinsic signals modulating cellular mechanisms to guide neuronal differentiation. However, little is known about the nature of these signals in the diencephalon, a complex brain region that processes and relays sensory and motor information to and from the cerebral cortex and subcortical structures. Morphogenetic signals from brain organizers regulate histogenetic processes such as cellular proliferation, migration, and differentiation. Sonic hedgehog (Shh) in the key signal of the ZLI, identified as the diencephalic organizer. Fgf15 , the mouse gene orthologous of human, chick, and zebrafish Fgf19 , is induced by Shh signal and expressed in the diencephalic Alar Plate progenitors during histogenetic developmental stages. This work investigates the role of Fgf15 signal in diencephalic development. In the absence of Fgf15, the complementary expression pattern of proneural genes: Ascl1 and Nng2, is disrupted and the GABAergic thalamic cells do not differentiate; in addition dorsal thalamic progenitors failed to exit from the mitotic cycle and to differentiate into neurons. Therefore, our findings indicate that Fgf15 is the Shh downstream signal to control thalamic regionalization, neurogenesis, and neuronal differentiation by regulating the expression and mutual segregation of neurogenic and proneural regulatory genes.
wnt signal specifies the intrathalamic limit and its organizer properties by regulating shh induction in the Alar PlateThe Journal of Neuroscience, 2013Co-Authors: Almudena Martinezferre, Maria Navarrogarberi, C G Bueno, Salvador MartinezAbstract:
The structural complexity of the brain depends on precise molecular and cellular regulatory mechanisms orchestrated by regional morphogenetic organizers. The thalamic organizer is the zona limitans intrathalamica (ZLI), a transverse linear neuroepithelial domain in the Alar Plate of the diencephalon. Because of its production of Sonic hedgehog, ZLI acts as a morphogenetic signaling center. Shh is expressed early on in the prosencephalic basal Plate and is then gradually activated dorsally within the ZLI. The anteroposterior positioning and the mechanism inducing Shh expression in ZLI cells are still partly unknown, being a subject of controversial interpretations. For instance, separate experimental results have suggested that juxtaposition of prechordal (rostral) and epichordal (caudal) neuroepithelium, anteroposterior encroachment of Alar lunatic fringe (L-fng) expression, and/or basal Shh signaling is required for ZLI specification. Here we investigated a key role of Wnt signaling in the molecular regulation of ZLI positioning and Shh expression, using experimental embryology in ovo in the chick. Early Wnt expression in the ZLI regulates Gli3 and L-fng to generate a permissive territory in which Shh is progressively induced by planar signals of the basal Plate.
Luis Puelles – 2nd expert on this subject based on the ideXlab platform
Topography of Somatostatin Gene Expression Relative to Molecular Progenitor Domains during Ontogeny of the Mouse HypothalamusFrontiers in Neuroanatomy, 2011Co-Authors: Nicanor Morales-delgado, Luis Puelles, Sylvia M Bardet, Paloma Merchán, José Luis Ferran, Carmen DíazAbstract:
The hypothalamus comprises Alar, basal, and floor Plate developmental compartments. Recent molecular data support a rostrocaudal subdivision into rostral (terminal) and caudal (peduncular) halves. In this context, the distribution of neuronal populations expressing somatostatin (Sst) mRNA was analyzed in the developing mouse hypothalamus, comparing with the expression pattern of the genes Orthopedia (Otp), Distal-less 5 (Dlx5), Sonic Hedgehog (Shh), and Nk2 homeobox 1 (Nkx2.1). At embryonic day 10.5 (E10.5), Sst mRNA was first detectable in the anterobasal nucleus, a Nkx2.1-, Shh-, and Otp-positive basal domain. By E13.5, nascent Sst expression was also related to two additional Otp-positive domains within the Alar Plate and one in the basal Plate. In the Alar Plate, Sst-positive cells were observed in rostral and caudal ventral subdomains of the Otp-positive paraventricular complex. An additional basal Sst-expressing cell group was found within a longitudinal Otp-positive periretromamillary band that separates the retromamillary area from tuberal areas. Apart of subsequent growth of these initial populations, at E13.5 and E15.5 some Sst-positive derivatives migrate tangentially into neighboring regions. A subset of cells produced at the anterobasal nucleus disperses ventralward into the shell of the ventromedial hypothalamic nucleus and the arcuate nucleus. Cells from the rostroventral paraventricular subdomain reach the suboptic nucleus, whereas a caudal contingent migrates radially into lateral paraventricular, perifornical, and entopeduncular nuclei. Our data provide a topologic map of molecularly defined progenitor areas originating a specific neuron type during early hypothalamic development. Identification of four main separate sources helps to understand causally its complex adult organization.
Conserved pattern of OTP-positive cells in the paraventricular nucleus and other hypothalamic sites of tetrapods.Brain research bulletin, 2007Co-Authors: Sylvia M Bardet, Margaret Martinez-de-la-torre, R Glenn Northcutt, John L R Rubenstein, Luis PuellesAbstract:
The paraventricular nucleus complex (Pa) is a component of central neural circuitry that regulates several homeostatic variables. The paraventricular nucleus is composed of magnocellular neurons that project to the posterior pituitary and parvicellular neurons that project to numerous sites in the central nervous system. According to the revised prosomeric model, the paraventricular nucleus is located caudal to the eye stalk along the rostrocaudal dimension of the dorsal hypothalamic Alar Plate. Caudally, the paraventricular nucleus abuts the prethalamus (prosomere 3), and the entire complex is flanked ventrally and dorsally by Dlx5-expressing domains of the Alar Plate. The homeodomain transcription factor Orthopedia (Otp) is expressed in several separate hypothalamic sites: the paraventricular nucleus, perimammillary region and arcuate nucleus. In this study, we compared Otp expression in the hypothalamus of mouse (Mus musculus), chick (Gallus gallus), frog (Rana perezi) and axolotol (Ambystoma mexicanum), using immunohistochemical and in situ hybridization techniques. In all cases, Otp-positive cells in the paraventricular nucleus were excluded from Dlx5-expressing adjacent domains. Other positive neuronal populations were observed in the arcuate nucleus and oblique perimammillary band. Expression in the medial amygdala appears to be continuous with the Otp-expressing paraventricular nucleus complex. This area is relatively unevaginated in the amphibian brains, barely evaginated in the chick, and fully evaginated in the mouse. These data led us to conclude that the expression pattern of Otp is topologically highly conserved in tetrapods and is plesiomorphic among chordates.
locus coeruleus neurons originate in Alar rhombomere 1 and migrate into the basal Plate studies in chick and mouse embryosThe Journal of Comparative Neurology, 2006Co-Authors: Pilar Aroca, Beatriz Lorentecanovas, Francisco R Mateos, Luis PuellesAbstract:
We investigated in the mouse and chick the neuroepithelial origin and development of the locus coeruleus (LoC), the most important noradrenergic neuronal population in the brain. We first studied the topography of the developing LoC in the hindbrain, using as markers the key noradrenergic marker gene Dbh and the transcription factors Phox2a and Phox2b (upstream of Dbh). In both mouse and chicken, LoC neurons first appear arranged linearly along the middle one-third of the Alar Plate of rhombomere 1 (r1), collinear to a reference ventricular longitudinal band that early on expresses Phox2a and Phox2b in the Alar Plate of r2 and later expands to r1. Double-labeling experiments with LoC markers (Dbh or Phox2a) and either Alar (Pax7 and Rnx3) or basal (Otp) genetic markers suggested that LoC cells migrate from their origin in the Alar Plate to a final position in the lateral basal Plate. To corroborate these suggestions experimentally and determine the precise origin of the LoC, we fate mapped the LoC in the chick at stage HH11 by using quail-chick homotopic grafts. The experimental results confirmed that the LoC originates in the Alar Plate throughout the rostrocaudal extent of r1 and ruled out a rostrocaudal translocation. They also corroborated a ventralward tangential migration of LoC cells into the lateral basal Plate, where the postmigratory LoC primordium is located. Comparisons with neighboring Alar r1-derived cell populations established that LoC neurons originate outside the cerebellum, in a matrix area intercalated dorsoventrally between the sources of the prospective vestibular and trigeminal columns. J. Comp. Neurol. 496:802– 818, 2006. © 2006 Wiley-Liss, Inc.
Fujio Murakami – 3rd expert on this subject based on the ideXlab platform
crossing the ventral midline causes neurons to change their response to floor Plate and Alar Plate attractive cues during transmedian migrationDevelopmental Biology, 2002Co-Authors: Hiroki Taniguchi, Fujio Murakami, Atsushi Tamada, Timothy E KennedyAbstract:
Neuronal migration is required for the establishment of specific neural structures, such as layers and nuclei. Neurons migrate along specific migratory routes toward their final destinations, sometimes across long distances. However, the cellular and molecular interactions that control neuronal migration are largely unknown. Here, we examined the mechanism underlying the transmedian migration of precerebellar neurons using a flat whole-mount preparation of the rat embryo. These neurons were initially attracted by the floor Plate (FP) at the ventral midline. However, after crossing the midline, they lost their responsiveness to the FP and became attracted by the Alar Plate (AP). Although the loss of responsiveness to FP cues was caused by an encounter of migrating cells with the FP, the gain of responsiveness to AP cues occurred irrespective of their encounter with the FP. These results identify a crucial change in the response of migrating cells to attractive guidance cues during the transmedian migration of precerebellar neurons.
Guidance of Circumferentially Growing Axons by Netrin-Dependent and -Independent Floor Plate Chemotropism in the Vertebrate BrainNeuron, 1996Co-Authors: Ryuichi Shirasaki, Christine Mirzayan, Marc Tessier-lavigne, Fujio MurakamiAbstract:
Abstract Netrin-1, a diffusible signal secreted by floor Plate cells at the ventral midline of the vertebrate CNS, can attract ventrally migrating axons and repel a subset of dorsally migrating axons in the spinal cord and rostral hindbrain in vitro. Whether netrin-1 can act as a global cue to guide all circumferentially migrating axons is, however, unknown. Here, we show that netrin-1 can attract Alar Plate axons that cross the floor Plate along its entire rostrocaudal axis. Dorsally directed axons forming the posterior commissure are, however, repelled by the floor Plate by a netrin-independent mechanism. These results suggest that netrin-1 functions as a global guidance cue for attraction to the midline. Moreover, floor Plate–mediated chemorepulsion may also operate generally to direct dorsal migrations, but its molecular basis may involve both netrin-dependent and -independent mechanisms.
Floor Plate chemoattracts crossed axons and chemorepels uncrossed axons in the vertebrate brain.Neuron, 1995Co-Authors: Atsushi Tamada, Ryuichi Shirasaki, Fujio MurakamiAbstract:
Abstract In the bilaterally symmetrical vertebrate CNS, all developing axons must choose between remaining on the same side of the midline or growing across it. The mechanism underlying this axonal pathfinding is, however, poorly understood. Here we demonstrate that the ventral midline floor Plate (FP) chemorepels two types of ipsilaterally projecting axons, one from the Alar Plate and another from the basal Plate in the mesencephalon. We further demonstrate that the FP chemoattracts contralaterally projecting myelencephalic as well as metencephalic axons. The FP at all axial levels displayed both chemoattractive and chemorepellent activities, suggesting that FP chemoattraction and chemorepulsion may be at work throughout the neuraxis. Chemotropic guidance by the FP may therefore play a key role in the establishment of neuronal projection laterality.