Chapter 5 Hox Genes in Neural Patterning and Circuit Formation in the Mouse Hindbrain

Narita, Yuichi; Rijli, Filippo M.

doi:10.1016/s0070-2153(09)88005-8

Cited by 68 publications

(62 citation statements)

References 130 publications

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“…However, it is likely that the broad strokes of connectivity in descending systems, including the pathways and regional termination areas of specific categories of descending axons, are established during development through stereotyped genetic mechanisms of neuron specification and target recognition. Thus there is strong reason to believe that certain principal features of connectivity are the same in neonates and adults (Di Bonito et al 2013a,b;Kasumacic et al 2012;Narita and Rijli 2009;Philippidou and Dasen 2013;Szokol et al 2011).…”

Section: General Overview Of Salient Resultsmentioning

confidence: 99%

Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse

Sivertsen

Glover

Perreault

2014

Journal of Neurophysiology

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Sivertsen MS, Glover JC, Perreault MC. Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse. J Neurophysiol 112: 1628 -1643, 2014. First published June 18, 2014 doi:10.1152/jn.00820.2013.-Using optical recording of synaptically mediated calcium transients and selective spinal lesions, we investigated the pattern of activation of spinal motoneurons (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord preparations from the neonatal mouse. Stimulation sites throughout the region where the pontine reticulospinal neurons reside reliably activated MNs at cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi-and contralateral to the stimulation site, similar in medial and lateral motor columns that contain trunk and limb MNs, respectively, and similar in the L2 and L5 segments that predominantly contain flexor and extensor MNs, respectively. In nonlesioned preparations, responses in both ipsi-and contralateral MNs followed individual stimuli in stimulus trains nearly one-to-one (with few failures). After unilateral hemisection at C1 on the same side as the stimulation, responses had substantially smaller magnitudes and longer latencies and no longer followed individual stimuli. After unilateral hemisection at C1 on the side opposite to the stimulation, the responses were also smaller, but their latencies were not affected. Thus we distinguish two pontine reticulospinal pathways to spinal MNs, one uncrossed and the other crossed, of which the uncrossed pathway transmits more faithfully and appears to be more direct. motor control; descending pathways; brain stem; spinal cord; trunk; limb THE MAMMALIAN RETICULOSPINAL system, consisting of the mesencephalic, pontine, and medullary reticulospinal pathways, is crucial for the control of skeletal musculature (Baker 2011;Kuypers 1964;Lemon 2008;Perreault and Glover 2013;Peterson 1979;Pettersson et al. 2007), but the neural mechanisms by which it initiates and regulates movement are far from understood.Electrical stimulation has been a key method in studying the organization of the mammalian reticulospinal system, revealing excitatory reticulospinal connections (mono-and polysynaptic) with axial motoneurons (MNs), proximal and distal limb MNs, and digit MNs in a variety of species (monkey: Davidson and Buford 2006;Riddle et al. 2009; cat: Drew and Rossignol 1990b;Galea et al. 2010;Grillner et al. 1968;Jankowska et al. 2003;Lloyd 1941;Peterson et al. 1979;Sprague and Chambers 1954;Wilson and Yoshida 1969; rat: Bolzoni et al. 2013; Floeter and Lev-Tov 1993;Umeda et al. 2010; and mouse: Alstermark and Ogawa 2004;Szokol et al. 2008). However, many studies have not differentiated among different areas of the reticular formation (RF) that project to the spinal cord. For example, stimulation of the medial longitudinal fasciculus (MLF), in which many (but certainly not all) reticulospinal axons project, is often used as a proxy for stimulating reticulospinal projectio...

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Section: General Overview Of Salient Resultsmentioning

confidence: 99%

Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse

Sivertsen

Glover

Perreault

2014

Journal of Neurophysiology

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“…Hence, other transcription factors should cooperate with Lim-HD proteins in patterning their growth. Hox code was shown to control axonal pathfinding in the spinal cord and hindbrain (Dasen et al, 2005;Geisen et al, 2008;Narita and Rijli, 2009;Watari-Goshima and Chisaka, 2011). It is possible that the diverse dA1 axonal tracts relay on different Hox genes.…”

Section: Possible Cues That Regulate Da1-axonal Projection Patternsmentioning

confidence: 99%

Axonal Patterns and Targets of dA1 Interneurons in the Chick Hindbrain

Kohl

Hadas²,

Klar³

et al. 2012

J. Neurosci.

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Hindbrain dorsal interneurons that comprise the rhombic lip relay sensory information and coordinate motor outputs. The progenitor dA1 subgroup of interneurons, which is formed along the dorsal-most region of the caudal rhombic lip, gives rise to the cochlear and precerebellar nuclei. These centers project sensory inputs toward upper-brain regions. The fundamental role of dA1 interneurons in the assembly and function of these brainstem nuclei is well characterized. However, the precise en route axonal patterns and synaptic targets of dA1 interneurons are not clear as of yet. Novel genetic tools were used to label dA1 neurons and trace their axonal trajectories and synaptic connections at various stages of chick embryos. Using dA1-specific enhancers, two contralateral ascending axonal projection patterns were identified; one derived from rhombomeres 6 -7 that elongated in the dorsal funiculus, while the other originated from rhombomeres 2-5 and extended in the lateral funiculus. Targets of dA1 axons were followed at later stages using PiggyBac-mediated DNA transposition. dA1 axons were found to project and form synapses in the auditory nuclei and cerebellum. Investigation of mechanisms that regulate the patterns of dA1 axons revealed a fundamental role of Lim-homeodomain (HD) proteins. Switch in the expression of the specific dA1 Lim-HD proteins Lhx2/9 into Lhx1, which is typically expressed in dB1 interneurons, modified dA1 axonal patterns to project along the routes of dB1 subgroup. Together, the results of this research provided new tools and knowledge to the assembly of trajectories and connectivity of hindbrain dA1 interneurons and of molecular mechanisms that control these patterns.

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“…The expression of Hox genes is sustained in the CNC, VNLL and SOC up to postnatal stages (Narita and Rijli 2009;Di Bonito et al 2013b). In postmitotic neurons, these transcription factors were shown to participate in the regulation of neuronal migration and axon pathfinding, including topographic connectivity mapping (Oury et al 2006;Geisen et al 2008;Di Meglio et al 2013).…”

Section: Embryonic Origin Of the Auditory Hindbrainmentioning

confidence: 99%

The emerging framework of mammalian auditory hindbrain development

et al. 2015

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A defining feature of the mammalian auditory system is the extensive processing of sound information in numerous ultrafast and temporally precise circuits in the hindbrain. By exploiting the experimental advantages of mouse genetics, recent years have witnessed an impressive advance in our understanding of developmental mechanisms involved in the formation and refinement of these circuits. Here, we will summarize the progress made in four major fields: the dissection of the rhombomeric origins of auditory hindbrain nuclei; the molecular repertoire involved in circuit formation such as Hox transcription factors and the Eph-ephrin signaling system; the timeline of functional circuit assembly; and the critical role of spontaneous activity for circuit refinement. In total, this information provides a solid framework for further exploration of the factors shaping auditory hindbrain circuits and their specializations. A comprehensive understanding of the developmental pathways and instructive factors will also offer important clues to the causes and consequences of hearing-loss related disorders, which represent the most common sensory impairment in humans.

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Chapter 5 Hox Genes in Neural Patterning and Circuit Formation in the Mouse Hindbrain

Cited by 68 publications

References 130 publications

Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse

Organization of pontine reticulospinal inputs to motoneurons controlling axial and limb muscles in the neonatal mouse

Axonal Patterns and Targets of dA1 Interneurons in the Chick Hindbrain

The emerging framework of mammalian auditory hindbrain development

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