A Hox Regulatory Network Establishes Motor Neuron Pool Identity and Target-Muscle Connectivity

Dasen, Jeremy S.; Tice, Bonnie C.; Brenner-Morton, Susan; Jessell, Thomas M.

doi:10.1016/j.cell.2005.09.009

Cited by 413 publications

(540 citation statements)

References 42 publications

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“…S3). The specification of gamma, and by inference, alpha motor neuron identity may therefore be a late event that occurs long after motor pool identities have been established (6,8,10,27). Motor neuron pool identities are initiated by the actions of a complex Hox protein repressor network, such that specific pool fates depend critically on the precise spectrum of Hox proteins expressed by a set of motor neurons (6).…”

Section: Discussionmentioning

confidence: 99%

“…The lateral motor column (LMC) neurons that project their axons to limb muscles can be further subdivided into divisional and pool subclasses that, together, specify the pattern of target muscle connectivity (4,5). The sequential steps involved in controlling motor neuron subtype identities and target projections are programmed through the cell-type selectivity of transcription factor expression, notably members of the Hox, LIM, Nkx6, and ETS families (6)(7)(8)(9)(10). Thus combinatorial programs of transcription factor expression appear to provide the fundamental logic of spinal motor neuron diversification and connectivity to specific peripheral muscle targets.…”

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confidence: 99%

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Gamma and alpha motor neurons distinguished by expression of transcription factor Err3

Friese

Kaltschmidt

Ladle

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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188

255

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Spinal motor neurons are specified to innervate different muscle targets through combinatorial programs of transcription factor expression. Whether transcriptional programs also establish finer aspects of motor neuron subtype identity, notably the prominent functional distinction between alpha and gamma motor neurons, remains unclear. In this study, we identify DNA binding proteins with complementary expression profiles in alpha and gamma motor neurons, providing evidence for molecular distinctions in these two motor neuron subtypes. The transcription factor Err3 is expressed at high levels in gamma but not alpha motor neurons, whereas the neuronal DNA binding protein NeuN marks alpha but not gamma motor neurons. Signals from muscle spindles are needed to support the differentiation of Err3 on /NeuN off presumptive gamma motor neurons, whereas direct proprioceptive sensory input to a motor neuron pool is apparently dispensable. Together, these findings provide evidence that transcriptional programs define functionally distinct motor neuron subpopulations, even within anatomically defined motor pools.motor neuron ͉ spinal cord ͉ transcription factors N euronal diversity underlies many features of central nervous system (CNS) organization and function. Neurons located within different regions of the CNS typically exhibit distinct morphologies and patterns of connectivity that help to determine their physiological functions. Within a single region, neurons that serve closely related functions can be further subdivided, both anatomically and physiologically. The retina, for example, contains multiple subclasses of ganglion and amacrine neurons that are distinguishable by position, patterns of dendritic arborization, and their role in visual processing (1, 2). Similarly, the cerebral cortex contains many local circuit interneurons, each with specialized anatomy, circuitry, and physiology (3). Little is known, however, about how such fine distinctions in CNS neuronal subtype identity and connectivity are assigned.The spinal cord represents a region of the CNS where the diversity of neuronal subtypes has been shown to emerge as a consequence of the expression of intrinsic molecular determinants, acting in a hierarchical manner to assign subtype identities to a generic set of motor neurons (4, 5). The motor neurons that project to skeletal muscle targets can be subdivided into distinct columnar subgroups, each projecting to a different target domain-axial, body wall, and limb targets. The lateral motor column (LMC) neurons that project their axons to limb muscles can be further subdivided into divisional and pool subclasses that, together, specify the pattern of target muscle connectivity (4, 5). The sequential steps involved in controlling motor neuron subtype identities and target projections are programmed through the cell-type selectivity of transcription factor expression, notably members of the Hox, LIM, Nkx6, and ETS families (6-10). Thus combinatorial programs of transcription factor expression appear to provide...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Gamma and alpha motor neurons distinguished by expression of transcription factor Err3

Friese

Kaltschmidt

Ladle

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

188

255

View full text Add to dashboard Cite

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“…In the spinal cord, motor neuron columnar fate (i.e., rostrocaudal motor neuron identity) is assigned through a Hox transcriptional regulatory network that is induced by graded fibroblast growth factor signaling (Dasen et al, 2003(Dasen et al, , 2005. There is increasing evidence for an analogous process in the telencepha-lon; fibroblast growth factor signaling also participates in rostralcaudal patterning of the entire telencephalon through regulating the graded expression of transcription factors such as Couptf1, Emx2, Dbx1, and Sp8 Storm et al, 2006).…”

Section: The Cge Contains the Caudal Extension Of Lge And Mge Progenimentioning

confidence: 99%

Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes

Flames¹,

Pla²,

Gelman³

et al. 2007

J. Neurosci.

513

780

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The mammalian telencephalon is considered the most complex of all biological structures. It comprises a large number of functionally and morphologically distinct types of neurons that coordinately control most aspects of cognition and behavior. The subpallium, for example, not only gives rise to multiple neuronal types that form the basal ganglia and parts of the amygdala and septum but also is the origin of an astonishing diversity of cortical interneurons. Despite our detailed knowledge on the molecular, morphological, and physiological properties of most of these neuronal populations, the mechanisms underlying their generation are still poorly understood. Here, we comprehensively analyzed the expression patterns of several transcription factors in the ventricular zone of the developing subpallium in the mouse to generate a detailed molecular map of the different progenitor domains present in this region. Our study demonstrates that the ventricular zone of the mouse subpallium contains at least 18 domains that are uniquely defined by the combinatorial expression of several transcription factors. Furthermore, the results of microtransplantation experiments in vivo corroborate that anatomically defined regions of the mouse subpallium, such as the medial ganglionic eminence, can be subdivided into functionally distinct domains.

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“…Since Hox genes function in late aspects of neuronal specification and axon morphogenesis (Jungbluth et al 1999;Liu et al 2001;Merritt and Whitington 2002;Miguel-Aliaga and Thor 2004;Dasen et al 2005), it seems possible that regulation of Hox genes by PcG genes may be important for aspects of post-mitotic neuronal morphogenesis, including dendrite development. We have found that the PcG genes esc and E(z) are required for proper down-regulation of BX-C Hox gene expression in class IV neurons.…”

Section: A Role For Polycomb Group Genes In Neuronal Developmentmentioning

confidence: 99%

Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites

Parrish¹,

Emoto²,

Jan³

2007

Genes Dev.

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Dendritic fields are important determinants of neuronal function. However, how neurons establish and then maintain their dendritic fields is not well understood. Here we show that Polycomb group (PcG) genes are required for maintenance of complete and nonoverlapping dendritic coverage of the larval body wall by Drosophila class IV dendrite arborization (da) neurons. In esc, Su(z)12, or Pc mutants, dendritic fields are established normally, but class IV neurons display a gradual loss of dendritic coverage, while axons remain normal in appearance, demonstrating that PcG genes are specifically required for dendrite maintenance. Both multiprotein Polycomb repressor complexes (PRCs) involved in transcriptional silencing are implicated in regulation of dendrite arborization in class IV da neurons, likely through regulation of homeobox (Hox) transcription factors. We further show genetic interactions and association between PcG proteins and the tumor suppressor kinase Warts (Wts), providing evidence for their cooperation in multiple developmental processes including dendrite maintenance.[Keywords: Drosophila; neuron; dendrite; Polycomb; homeobox; tumor suppressor] Supplemental material is available at http://www.genesdev.org. Received November 20, 2006; revised version accepted February 26, 2007. Dendrite arborization patterns are important for neuronal function and proper wiring of neuronal circuitry. Moreover, sensory perception in some cases depends on complete and nonredundant coverage of the receptive field by dendrites of functionally related neurons, a phenomenon known as tiling. For example, many types of neurons tile the mammalian retina, most likely to ensure efficient and unambiguous representation of the visual field. At least 11 distinct physiological classes of rabbit retinal ganglion cells (RGCs) cover their receptive field nonredundantly by avoiding overlap between dendrites of a single neuron as well as between dendrites of the same type of neurons, whereas dendrites of different types of neurons freely cross one another (Wassle et al. 1978(Wassle et al. , 1983Rockhill et al. 2002). Similarly, >20 classes of amacrine cells in the rabbit retina can be distinguished on the basis of dendrite morphology, and many of these classes of amacrine cells appear to tile the retina. Sensory neurons in Manduca, Drosophila, and the leech Hirudu medicinalis also exhibit tiling, suggesting that tiling may be a general mechanism to organize dendritic fields Grueber and Jan 2004).Once neurons tile their receptive field and achieve complete coverage during development, the tiling is maintained even as the territory changes; for example, as the animal grows in size. Whereas like-repels-like homotypic repulsion is one mechanism important for the establishment of receptive fields (Grueber et al. 2003b), how tiling is maintained after the establishment of the dendritic field is not well understood. Underscoring the potential physiological significance of the maintenance of dendritic fields, dendrites of layer III cortical ...

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A Hox Regulatory Network Establishes Motor Neuron Pool Identity and Target-Muscle Connectivity

Cited by 413 publications

References 42 publications

Gamma and alpha motor neurons distinguished by expression of transcription factor Err3

Gamma and alpha motor neurons distinguished by expression of transcription factor Err3

Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes

Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites

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