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      Cellular and Molecular Underpinnings of Neuronal Assembly in the Central Auditory System during Mouse Development


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          During development, the organization of the auditory system into distinct functional subcircuits depends on the spatially and temporally ordered sequence of neuronal specification, differentiation, migration and connectivity. Regional patterning along the antero-posterior axis and neuronal subtype specification along the dorso-ventral axis intersect to determine proper neuronal fate and assembly of rhombomere-specific auditory subcircuits. By taking advantage of the increasing number of transgenic mouse lines, recent studies have expanded the knowledge of developmental mechanisms involved in the formation and refinement of the auditory system. Here, we summarize several findings dealing with the molecular and cellular mechanisms that underlie the assembly of central auditory subcircuits during mouse development, focusing primarily on the rhombomeric and dorso-ventral origin of auditory nuclei and their associated molecular genetic pathways.

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          Math1: an essential gene for the generation of inner ear hair cells.

          The mammalian inner ear contains the cochlea and vestibular organs, which are responsible for hearing and balance, respectively. The epithelia of these sensory organs contain hair cells that function as mechanoreceptors to transduce sound and head motion. The molecular mechanisms underlying hair cell development and differentiation are poorly understood. Math1, a mouse homolog of the Drosophila proneural gene atonal, is expressed in inner ear sensory epithelia. Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells. This gene is thus required for the genesis of hair cells.
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            Hox genes: choreographers in neural development, architects of circuit organization.

            The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This Review highlights the functions and mechanisms of Hox gene networks and their multifaceted roles during neuronal specification and connectivity. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum.

              The molecular machinery governing glutamatergic-GABAergic neuronal subtype specification is unclear. Here we describe a cerebellar mutant, cerebelless, which lacks the entire cerebellar cortex in adults. The primary defect of the mutant brains was a specific inhibition of GABAergic neuron production from the cerebellar ventricular zone (VZ), resulting in secondary and complete loss of external germinal layer, pontine, and olivary nuclei during development. We identified the responsible gene, Ptf1a, whose expression was lost in the cerebellar VZ but was maintained in the pancreas in cerebelless. Lineage tracing revealed that two types of neural precursors exist in the cerebellar VZ: Ptf1a-expressing and -nonexpressing precursors, which generate GABAergic and glutamatergic neurons, respectively. Introduction of Ptf1a into glutamatergic neuron precursors in the dorsal telencephalon generated GABAergic neurons with representative morphological and migratory features. Our results suggest that Ptf1a is involved in driving neural precursors to differentiate into GABAergic neurons in the cerebellum.

                Author and article information

                Front Neural Circuits
                Front Neural Circuits
                Front. Neural Circuits
                Frontiers in Neural Circuits
                Frontiers Media S.A.
                19 April 2017
                : 11
                : 18
                Université Côte d'Azur, CNRS, Inserm, iBV Nice, France
                Author notes

                Edited by: Catherine Carr, University of Maryland, College Park, USA

                Reviewed by: Karina S. Cramer, University of California, Irvine, USA; Daniel Llano, University of Illinois at Urbana–Champaign, USA

                *Correspondence: Michèle Studer michele.studer@ 123456unice.fr
                Copyright © 2017 Di Bonito and Studer.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 21 December 2016
                : 01 March 2017
                Page count
                Figures: 8, Tables: 1, Equations: 0, References: 175, Pages: 25, Words: 19455
                Funded by: Agence Nationale de la Recherche 10.13039/501100001665
                Award ID: ANR-15-CE15-0016-01

                central auditory system,rhombomeres,dv molecular determinants,hox genes,mouse lineage tracing


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