Aroca Tejedor,  Pilar

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Aroca Tejedor, Pilar

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Aroca Tejedor, Pilar

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Anatomía Humana y Psicobiología

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Open Access
Expression Patterns of Irx Genes in the Developing Chick Inner Ear
(Laszlo Zaborsky - Springer, 2016-10-25) Cardeña-Núñez, Sheila; Sánchez-Guardado, Luis Óscar; Corral-San-Miguel, Rubén; Rodríguez-Gallardo, Lucía; Puelles, Luis; Hidalgo-Sánchez, Matías; Aroca Tejedor, Pilar; Marín San Leandro, Faustino; Anatomía Humana y Psicobiología
The vertebrate inner ear is a complex three-dimensional sensorial structure with auditory and vestibular functions. The molecular patterning of the developing otic epithelium creates various positional identities, consequently leading to the stereotyped specification of each neurosensory and non-sensory element of the membranous labyrinth. The Iroquois (Iro/Irx) genes, clustered in two groups (A: Irx1, Irx2, and Irx4; and B: Irx3, Irx5, and Irx6), encode for transcriptional factors involved directly in numerous patterning processes of embryonic tissues in many phyla. This work presents a detailed study of the expression patterns of these six Irx genes during chick inner ear development, paying particular attention to the axial specification of the otic anlagen. The Irx genes seem to play different roles at different embryonic periods. At the otic vesicle stage (HH18), all the genes of each cluster are expressed identically. Both clusters A and B seem involved in the specification of the lateral and posterior portions of the otic anlagen. Cluster B seems to regulate a larger area than cluster A, including the presumptive territory of the endolymphatic apparatus. Both clusters seem also to be involved in neurogenic events. At stages HH24/25-HH27, combinations of IrxA and IrxB genes participate in the specification of most sensory patches and some non-sensory components of the otic epithelium. At stage HH34, the six Irx genes show divergent patterns of expression, leading to the final specification of the membranous labyrinth, as well as to cell differentiation.
Open Access
De novo mutations in PLXND1 and REV3L cause Mobius syndrome
(2015-06-12) Tomas-Roca, Laura; Tsaalbi-Shtylik, Anastasia; Jansen, Jacob G.; Singh, Manvendra K.; Epstein, Jonathan A.; Altunoglu, Umut; Verzijl, Harriette; Soria, Laura; Beusekom, Ellen van; Roscioli, Tony; Iqbal, Zafar; Gilissen, Christian; Hoischen, Alexander; de Brouwer, Arjan P.M.; Erasmus, Corrie; Schubert, Dirk; Brunner, Han; Perez Aytes, Antonio; Kayserili, Hulya; Carta, Arturo; de Wind, Niels; Padberg, George W.; Bokhoven, Hans van; Aroca Tejedor, Pilar; Marín San Leandro, Faustino; Anatomía Humana y Psicobiología; Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB,The Netherlands.; Department of Human Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.; Department of Cell andDevelopmental Biology, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 9-105 SCTR, 3400 Civic Center Boulevard,Philadelphia, Pennsylvania 19104, USA; Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical SchoolSingapore, National Heart Center Singapore, 8 College Road, Singapore 169857, Singapore; Medical Genetics Department, Istanbul Medical Faculty,Istanbul University, Millet Caddesi, Capa, Fatih 34093, Turkey.; Department of Neurology, Radboud University Medical Center, Donders Institute for Brain,Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands.; The Kinghorn Centre for Clinical Genomics, Garvan Institute of MedicalResearch, Sydney, New South Wales 2010, Australia; Department of Human Genetics, Radboud University Medical Center, Radboud Institute for MolecularLife Sciences (RIMLS), PO Box 9101, Nijmegen 6500 HB, The Netherlands.; Department of Cognitive Neuroscience, Radboud University Medical Center,Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands; Department of Clinical Genetics, MaastrichtUniversity Medical Center, PO Box 5800, Maastricht 6200AZ, The Netherlands.; Dysmorphology and Reproductive Genetics Unit, Moebius SyndromeFoundation of Spain, University Hospital LA FE, Valencia 46540, Spain.; Ophthalmology Unit, Department of Biomedical, Biotechnological and TranslationalSciences (S.Bi.Bi.T.), University of Parma, via Gramsci 14, 43126, Parma, Italy
Mo ̈bius syndrome (MBS) is a neurological disorder that is characterized by paralysis of thefacial nerves and variable other congenital anomalies. The aetiology of this syndrome hasbeen enigmatic since the initial descriptions by von Graefe in 1880 and by Mo ̈bius in 1888,and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology.Here, we reportde novomutations affecting two genes,PLXND1andREV3Lin MBS patients.PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development:neural migration and DNA translesion synthesis, essential for the replication of endogenouslydamaged DNA, respectively. Interestingly, analysis ofPlxnd1andRev3lmutant mice showsthat disruption of these separate pathways converge at the facial branchiomotor nucleus,affecting either motoneuron migration or proliferation. The finding thatPLXND1andREV3Lmutations are responsible for a proportion of MBS patients suggests thatde novomutations inother genes might account for other MBS patients
Open Access
Multiple regionalized genes and their putative Networks in the interpeduncular nucleus suggest complex mechanisms of neuron development and axon guidance
(Frontiers Media, 2021-02-16) García-Guillén, Isabel M.; Puelles López, Luis; Alonso Fuentes, Antonia; Aroca Tejedor, Pilar; Marín San Leandro, Faustino; Anatomía Humana y Psicobiología
The interpeduncular nucleus (IPN) is a highly conserved limbic structure in the vertebrate brain, located in the isthmus and rhombomere 1. It is formed by various populations that migrate from different sites to the distinct domains within the IPN: the prodromal, rostral interpeduncular, and caudal interpeduncular nuclei. The aim here was to identify genes that are differentially expressed across these domains, characterizing their putative functional roles and interactions. To this end, we screened the 2,038 genes in the Allen Developing Mouse Brain Atlas database expressed at E18.5 and we identified 135 genes expressed within the IPN. The functional analysis of these genes highlighted an overrepresentation of gene families related to neuron development, cell morphogenesis and axon guidance. The interactome analysis within each IPN domain yielded specific networks that mainly involve members of the ephrin/Eph and Cadherin families, transcription factors and molecules related to synaptic neurotransmission. These results bring to light specific mechanisms that might participate in the formation, molecular regionalization, axon guidance and connectivity of the different IPN domains. This genoarchitectonic model of the IPN enables data on gene expression and interactions to be integrated and interpreted, providing a basis for the further study of the connectivity and function of this poorly understood nuclear complex under both normal and pathological conditions.
Open Access
Molecular Segmentation of the Spinal Trigeminal Nucleus in the Adult Mouse Brain
(Frontiers Media, 2021-12-10) García-Guillén, Isabel M.; Martínez-de-la-Torre, Margaret; Puelles, Luis; Aroca Tejedor, Pilar; Marín San Leandro, Faustino; Anatomía Humana y Psicobiología
The trigeminal column is a hindbrain structure formed by second order sensory neurons that receive afferences from trigeminal primary (ganglionic) nerve fibers. Classical studies subdivide it into the principal sensory trigeminal nucleus located next to the pontine nerve root, and the spinal trigeminal nucleus which in turn consists of oral, interpolar and caudal subnuclei. On the other hand, according to the prosomeric model, this column would be subdivided into segmental units derived from respective rhombomeres. Experimental studies have mapped the principal sensory trigeminal nucleus to pontine rhombomeres (r) r2-r3 in the mouse. The spinal trigeminal nucleus emerges as a plurisegmental formation covering several rhombomeres (r4 to r11 in mice) across pontine, retropontine and medullary hindbrain regions. In the present work we reexamined the issue of rhombomeric vs. classical subdivisions of this column. To this end, we analyzed its subdivisions in an AZIN2-lacZ transgenic mouse, known as a reference model for hindbrain topography, together with transgenic reporter lines for trigeminal fibers. We screened as well for genes differentially expressed along the axial dimension of this structure in the adult and juvenile mouse brain. This analysis yielded genes from multiple functional families that display transverse domains fitting the mentioned rhombomeric map. The spinal trigeminal nucleus thus represents a plurisegmental structure with a series of distinct neuromeric units having unique combinatorial molecular profiles.
Metadata only
Caracterización y función de dopacromo tautomerasa, una nueva enzima reguladora de la melanogénesis [Microforma].
(Murcia : Universidad de Murcia,, 1991) Aroca Tejedor, Pilar
Open Access
Netrin-1/DCC signaling differentially regulates the migration of Pax7, Nkx6.1, Irx2, Otp and Otx2 cell populations in the developing interpeduncular nucleus
(Frontiers Media, 2020-10-20) García-Guillén, Isabel M.; Morales-Delgado, Nicanor; Andrés, Belén; Puelles López, Luis; López-Bendito, Guillermina; Alonso Fuentes, Antonia; Aroca Tejedor, Pilar; Marín San Leandro, Faustino; Anatomía Humana y Psicobiología
The interpeduncular nucleus (IPN) is a hindbrain structure formed by three main subdivisions, the prodromal (Pro) domain located at the isthmus (Ist), and the rostral and caudal interpeduncular domains (IPR, IPC) within rhombomere 1 (r1). Various cell populations can be detected in the IPN through the expression of the Nkx6.1, Otp, Otx2, Pax7, and/or Irx2 transcription factors. These cell populations follow independent dorsoventral tangential and radial migratory routes targeting the ventral paramedian region of Ist and r1. Here we set out to examine the influence of the Netrin-1/DCC pathway on these migrations, since it is known to regulate other processes of neuronal migration in the brain. To this end, we analyzed IPN development in late gestational wild-type and DCC-/- mice, using mainly in situ hybridization (ISH) to identify the cells expressing each of the aforementioned genes. We found that the migration of Nkx6.1 + and Irx2 + cells into the Pro domain was strongly disrupted by the loss of DCC, as occurred with the migration of Pax7 +, Irx2 +, and Otp + cells that would normally form the IPR. In addition, there was mild impairment of the migration of the Pax7 + and Otx2 + cells that form the IPC. These results demonstrate that the Netrin-1/DCC signaling pathway is involved in the migration of most of the IPN populations, mainly affecting those of the Pro and IPR domains of this nucleus. There are psychiatric disorders that involve the medial habenula (mHb)-IPN system, so that this experimental model could provide a basis to study their neurodevelopmental etiology.
Open Access
Molecular identity of the lateral lemniscus nuclei in the adult mouse brain
(Frontiers Media, 2023-03-09) García-Guillén, Isabel M.; Aroca Tejedor, Pilar; Marín San Leandro, Faustino; Anatomía Humana y Psicobiología
The dorsal (DLL), intermediate (ILL), and ventral (VLL) lateral lemniscus nuclei are relay centers in the central auditory pathway of the brainstem, commonly referred to as the lateral lemniscus nuclei (LLN). The LLN are situated in the prepontine and pontine hindbrain, from rhombomeres 1 to 4, extending from the more rostral DLL to the caudal VLL, with the ILL lying in between. These nuclei can be distinguished morphologically and by topological and connectivity criteria, and here, we set out to further characterize the molecular nature of each LLN. We searched in situ hybridization studies in the Allen Mouse Brain Atlas for genes differentially expressed along the rostrocaudal axis of the brainstem, identifying 36 genes from diverse functional families expressed in the LLN. Available information in the databases indicated that 7 of these 36 genes are either associated with or potentially related to hearing disorders. In conclusion, the LLN are characterized by specific molecular profiles that reflect their rostrocaudal organization into the three constituent nuclei. This molecular regionalization may be involved in the etiology of some hearing disorders, in accordance with previous functional studies of these genes.
Metadata only
Caracterización y función de dopacromo tautomerasa : una nueva enzima reguladora de la melanogénesis / Pilar Aroca Tejedor ; directores Francisco Solano Muñoz, José Carlos García-Borrón.
(Murcia : Universidad de Murcia, Facultad de Medicina,, 1991) Aroca Tejedor, Pilar