Victor Vendrell

Fundación Medina

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Thomas Schimmang

Instituto de Biomedicina y Genética Molecular de Valladolid

Iris López‐Hernández

Instituto de Biomedicina y Genética Molecular de Valladolid

Marı́a Teresa Alonso

Instituto de Biomedicina y Genética Molecular de Valladolid

Fernando Giráldez

Barcelona Biomedical Research Park

María Beatriz Durán Alonso

Universidad de Valladolid

Paula Murphy

Trinity College Dublin

Elena Domínguez‐Frutos

Universidad de Valladolid

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Yolanda Álvarez

Instituto de Biomedicina y Genética Molecular de Valladolid

Laura C. Zelarayán

Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103

Breandán N. Kennedy

University College Dublin

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Consejo Superior de Investigaciones Científicas

Universidad de Valladolid

Instituto de Biomedicina y Genética Molecular de Valladolid

University College Dublin

Universidad Autónoma de Madrid

Universität Hamburg

University of Edinburgh

Trinity College Dublin

Instituto de Salud Carlos III

Pompeu Fabra University

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N-mycControls Proliferation, Morphogenesis, and Patterning of the Inner Ear

Journal of Neuroscience (2011)

Elena Domínguez‐Frutos Iris López‐Hernández Victor Vendrell Joana Neves Micaela Gallozzi

Myc family members play crucial roles in regulating cell proliferation, size, and differentiation during organogenesis. Both N-myc and c-myc are expressed throughout inner ear development. To address their function in the mouse inner ear, we generated mice with conditional deletions in either N-myc or c-myc . Loss of c-myc in the inner ear causes no apparent defects, whereas inactivation of N-myc results in reduced growth caused by a lack of proliferation. Reciprocally, the misexpression of N-myc in the inner ear increases proliferation. Morphogenesis of the inner ear in N-myc mouse mutants is severely disturbed, including loss of the lateral canal, fusion of the cochlea with the sacculus and utriculus, and stunted outgrowth of the cochlea. Mutant cochleas are characterized by an increased number of cells exiting the cell cycle that express the cyclin-dependent kinase inhibitor p27 Kip1 and lack cyclin D1, both of which control the postmitotic state of hair cells. Analysis of different molecular markers in N-myc mutant ears reveals the development of a rudimentary organ of Corti containing hair cells and the underlying supporting cells. Differentiated cells, however, fail to form the highly ordered structure characteristic for the organ of Corti but appear as rows or clusters with an excess number of hair cells. The Kölliker's organ, a transient structure neighboring the organ of Corti and a potential source of ectopic hair cells, is absent in the mutant ears. Collectively, our data suggest that N-myc regulates growth, morphogenesis, and pattern formation during the development of the inner ear.

10.1523/jneurosci.0785-11.2011

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Citations (47)

Tissue-specific requirements for FGF8 during early inner ear development

Mechanisms of Development (2009)

Elena Domínguez‐Frutos Victor Vendrell Yolanda Álvarez Laura C. Zelarayán Iris López‐Hernández

FGF8

Otic vesicle

Ectopic expression

10.1016/j.mod.2009.07.004

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Citations (22)

Roles of Wnt8a during formation and patterning of the mouse inner ear

Mechanisms of Development (2012)

Victor Vendrell Citlali Vázquez‐Echeverría Iris López‐Hernández María Beatriz Durán Alonso Salvador Martı́nez

Otic vesicle

Hindbrain

10.1016/j.mod.2012.09.009

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Citations (23)

Duplication and Divergence of Zebrafish CRALBP Genes Uncovers Novel Role for RPE- and Müller-CRALBP in Cone Vision

Investigative Ophthalmology & Visual Science (2008)

Ross F. Collery Sarah McLoughlin Victor Vendrell Jennifer M. Finnegan John W. Crabb

purpose. During vertebrate phototransduction 11-cis-retinal is isomerized to all-trans-retinal. Light sensitivity is restored by recombination of apo-opsin with 11-cis-retinal to regenerate visual pigments. The conversion of all-trans retinal back to 11-cis-retinal is known as the visual cycle. Within the retina, cellular retinal-binding protein (CRALBP) is abundantly expressed in the retinal pigment epithelium (RPE) and Müller glia. CRALBP expressed in the RPE is known to facilitate the rate of the rod visual cycle. Recent evidence suggests a role for Müller glia in an alternate cone visual cycle. In this study, the role of RPE- and Müller-CRALBP in cone vision was characterized. methods. The CRALBP orthologues rlbp1a and rlbp1b were identified in zebrafish by bioinformatic methods. The spatial and developmental expression of rlbp1a and rlbp1b was determined by in situ hybridization and immunohistochemistry. Depletion of the expression of the corresponding Cralbp a and Cralbp b proteins was achieved by microinjection of antisense morpholinos. Visual function was analyzed in 5-day post fertilization (dpf) larvae using the optokinetic response assay. results. The zebrafish genome contains two CRALBP ohnologues, rlbp1a and rlbp1b. These genes have functionally diverged, exhibiting differential expression at 5 dpf in RPE and Müller glia, respectively. Depletion of CRALBP in the RPE or Müller glia results in abnormal cone visual behavior. conclusions. The results suggest that cone photoreceptors incorporate 11-cis-retinoids derived from the rod and cone visual cycles into their visual pigments and that Müller-CRALBP participates in the cone visual cycle.

Visual phototransduction

Muller glia

Opsin

Morpholino

10.1167/iovs.08-1957

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Citations (56)

Differential requirements for FGF3, FGF8 and FGF10 during inner ear development

Developmental Biology (2007)

Laura C. Zelarayán Victor Vendrell Yolanda Álvarez Elena Domínguez‐Frutos Thomas Theil

Otic vesicle

Hindbrain

FGF8

10.1016/j.ydbio.2007.05.033

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Citations (96)

Enological Suitability of Indigenous Yeast Strains for ‘Verdejo’ Wine Production

Foods (2023)

Jennifer Vázquez Ana María Mislata Victor Vendrell Carlos Moro Sergi de Lamo

The use of indigenous yeasts for the production of wines is a tool to defend the typicity of a particular region. The selection of appropriate indigenous yeasts ensures the maintenance of oenological characteristics by simulating spontaneous alcoholic fermentation (AF) while avoiding the risks of stuck or sluggish fermentations. In this study, autochthonous yeasts from Verdejo grape juice (Appellation of Origin Rueda) were selected, identified, and characterized to exploit the characteristics of the 'terroir'. The fermentation capacity of seven strains was studied individually at the laboratory scale. The most suitable strains (Saccharomyces cerevisiae: Sacch 1, Sacch 2, Sacch 4, and Sacch 6) and Sacch 6 co-inoculated with Metschnikowia pulcherrima were characterized at the pilot scale. The fermentation kinetics, bioproduct release, volatile composition, and sensory profile of the wines were evaluated. Significant differences were found, especially in the aroma profile. In particular, Sacch 6 and Sacch 6 co-inoculated with M. pulcherrima produced higher amounts of ethyl esters and acetates and lower amounts of higher alcohols than the spontaneous AF. Wines inoculated with indigenous yeasts had higher sensory scores for fruit aromas and overall rating. The selection of indigenous yeasts improved the aroma of Verdejo wines and could contribute to determining the wine typicity of the wine region.

10.3390/foods12091888

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Citations (7)

Inactivation of Fgf3 and Fgf4 within the Fgf3/Fgf4/Fgf15 gene cluster reveals their redundant requirement for mouse inner ear induction and embryonic survival

Developmental Dynamics (2021)

Laura C. Zelarayán Victor Vendrell Elena Domínguez‐Frutos Iris López‐Hernández Kiril Schimmang‐Alonso

Fibroblast growth factors (Fgfs) are required for survival and organ formation during embryogenesis. Fgfs often execute their functions redundantly. Previous analysis of Fgf3 mutants revealed effects on inner ear formation and embryonic survival with incomplete penetrance.Here, we show that presence of a neomycin resistance gene (neo) replacing the Fgf3 coding region leads to reduced survival during embryogenesis and an increased penetrance of inner ear defects. Fgf3neo/neo mutants showed reduced expression of Fgf4, which is positioned in close proximity to the Fgf3 locus in the mouse genome. Conditional inactivation of Fgf4 during inner ear development on a Fgf3 null background using Fgf3/4 cis mice revealed a redundant requirement between these Fgfs during otic placode induction. In contrast, inactivation of Fgf3 and Fgf4 in the pharyngeal region where both Fgfs are also co-expressed using a Foxg1-Cre driver did not affect development of the pharyngeal arches. However, these mutants showed reduced perinatal survival.These results highlight the importance of Fgf signaling during development. In particular, different members of the Fgf family act redundantly to guarantee inner ear formation and embryonic survival.

Penetrance

10.1002/dvdy.435

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Citations (3)

Induction of inner ear fate by FGF3

Development (2000)

Victor Vendrell Estela Carnicero Fernando Giráldez Marı́a Teresa Alonso Thomas Schimmang

ABSTRACT 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 vertebrates.

Ectopic expression

Otic vesicle

Embryonic Induction

10.1242/dev.127.10.2011

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Citations (130)

mab21l2 transgenics reveal novel expression patterns of mab21l1 and mab21l2, and conserved promoter regulation without sequence conservation

Developmental Dynamics (2011)

Maria L. Cederlund Victor Vendrell Maria E. Morrissey Jun Yin Peadar Ó Gaora

mab21l1 and mab21l2 paralogs have widespread and dynamic expression patterns during vertebrate development. Both genes are expressed in the developing eye, midbrain, neural tube, and branchial arches. Our goal was to identify promoter regions with activity in mab21l2 expression domains. Assays of mab21l2 promoter-EGFP constructs in zebrafish embryos confirm that constructs containing 7.2 or 4.9 kb of mab21l2 promoter region are sufficient to drive expression in known (e.g., tectum, branchial arches) and unexpected domains (e.g., lens and retinal amacrine cells). A comparative analysis identifies complementary and novel expression domains of endogenous mab21l2 (e.g., lens and ventral iridocorneal canal) and mab21l1 (e.g., retinal amacrine and ganglion cells). Interestingly, therefore, despite the absence of conserved non-coding elements, a 4.9-kb mab21l2 promoter is sufficient to recapitulate expression in tissues unique to mab21l1 or mab21l2.

Conserved sequence

10.1002/dvdy.22573

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Citations (13)

Requirements for FGF3 and FGF10 during inner ear formation

Development (2003)

Yolanda Álvarez Marı́a Teresa Alonso Victor Vendrell Laura C. Zelarayán Pablo Chamero

Members of the fibroblast growth factor (FGF) gene family control formation of the body plan and organogenesis in vertebrates. FGF3 is expressed in the developing hindbrain and has been shown to be involved in inner ear development of different vertebrate species, including zebrafish, Xenopus, chick and mouse. In the mouse, insertion of a neomycin resistance gene into the Fgf3 gene via homologous recombination results in severe developmental defects during differentiation of the otic vesicle. We have addressed the precise roles of FGF3 and other FGF family members during formation of the murine inner ear using both loss- and gain-of-function experiments. We generated a new mutant allele lacking the entire FGF3-coding region but surprisingly found no evidence for severe defects either during inner ear development or in the mature sensory organ, suggesting the functional involvement of other FGF family members during its formation. Ectopic expression of FGF10 in the developing hindbrain of transgenic mice leads to the formation of ectopic vesicles, expressing some otic marker genes and thus indicating a role for FGF10 during otic vesicle formation. Expression analysis of FGF10 during mouse embryogenesis reveals a highly dynamic pattern of expression in the developing hindbrain, partially overlapping with FGF3 expression and coinciding with formation of the inner ear. However, FGF10 mutant mice have been reported to display only mild defects during inner ear differentiation. We thus created double mutant mice for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for otic vesicle formation.

Otic vesicle

Hindbrain

Ectopic expression

10.1242/dev.00881

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Citations (198)