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      The Drosophila Hox gene Ultrabithorax acts in both muscles and motoneurons to orchestrate formation of specific neuromuscular connections

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          Abstract

          Hox genes are known to specify motoneuron pools in the developing vertebrate spinal cord and to control motoneuronal targeting in several species. However, the mechanisms controlling axial diversification of muscle innervation patterns are still largely unknown. We present data showing that the Drosophila Hox gene Ultrabithorax ( Ubx) acts in the late embryo to establish target specificity of ventrally projecting RP motoneurons. In abdominal segments A2 to A7, RP motoneurons innervate the ventrolateral muscles VL1-4, with VL1 and VL2 being innervated in a Wnt4-dependent manner. In Ubx mutants, these motoneurons fail to make correct contacts with muscle VL1, a phenotype partially resembling that of the Wnt4 mutant. We show that Ubx regulates expression of Wnt4 in muscle VL2 and that it interacts with the Wnt4 response pathway in the respective motoneurons. Ubx thus orchestrates the interaction between two cell types, muscles and motoneurons, to regulate establishment of the ventrolateral neuromuscular network.

          Abstract

          Summary: Ultrabithorax controls correct innervation of ventrolateral muscles by coordinating Wnt4 ligand expression in muscles with the signalling pathway response in motoneurons.

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          Most cited references64

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          Homeobox genes and axial patterning.

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            Molecular mechanisms of axon guidance.

            Axons are guided along specific pathways by attractive and repulsive cues in the extracellular environment. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules, including netrins, Slits, semaphorins, and ephrins. Guidance cues steer axons by regulating cytoskeletal dynamics in the growth cone through signaling pathways that are still only poorly understood. Elaborate regulatory mechanisms ensure that a given cue elicits the right response from the right axons at the right time but is otherwise ignored. With such regulatory mechanisms in place, a relatively small number of guidance factors can be used to generate intricate patterns of neuronal wiring.
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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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                Author and article information

                Journal
                Development
                Development
                DEV
                develop
                Development (Cambridge, England)
                The Company of Biologists Ltd
                0950-1991
                1477-9129
                1 January 2017
                1 January 2017
                : 144
                : 1
                : 139-150
                Affiliations
                Institute of Genetics, University of Mainz , Mainz 55128, Germany
                Author notes
                [*]

                Present address: COS Centre for Organismal Studies, University of Heidelberg, Heidelberg 69120, Germany

                [ ]Authors for correspondence ( technau@ 123456uni-mainz.de ; rogulja@ 123456uni-mainz.de )
                Author information
                http://orcid.org/0000-0002-8727-3882
                Article
                DEV143875
                10.1242/dev.143875
                5278631
                27913640
                518a2345-5cfd-405b-aa5f-a1c179d1325c
                © 2017. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 18 August 2016
                : 17 November 2016
                Funding
                Funded by: Deutsche Forschungsgemeinschaft, http://dx.doi.org/10.13039/501100001659;
                Award ID: RO 4137/2-1
                Award ID: TE130/9-3
                Award ID: GRK1044
                Categories
                209
                Research Article

                Developmental biology
                motoneurons,muscle innervation,segmental patterning,hox genes,wnt signalling pathway,drosophila

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