Emerging roles for HOX proteins in synaptogenesis

2018 ◽  
Vol 62 (11-12) ◽  
pp. 807-818 ◽  
Author(s):  
Françoise Gofflot ◽  
Benoit Lizen
Keyword(s):  
Cell Fate ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Target Selection ◽  
Axon Growth ◽  
Current Data ◽  
Cell Fate Specification ◽  
Hox Proteins ◽  
Circuit Formation ◽  
Vertebrate Central Nervous System

Neural circuit formation requires the intricate orchestration of multiple developmental events including cell fate specification, cell migration, axon guidance, dendritic growth, synaptic target selection, and synaptogenesis. The HOX proteins are well-known transcriptional regulators that control embryonic development. Investigations into their action in the vertebrate central nervous system have demonstrated pivotal roles in specifying neural subpopulations, but also in several successive steps required for the assembly of neuronal circuitry, such as neuron migration, axon growth and pathfinding and synaptic target selection. Several lines of evidence suggest that the HOX transcription factors could also regulate synaptogenesis processes even after the process of axonal and dendritic guidance has concluded. Here we will review the current data on HOX proteins in neural circuit formation in order to evaluate their potential roles in establishing neuronal connectivity with specific emphasis on synapse formation and maturation.

Glial cell fate specification modulated by the bHLH gene Hes5 in mouse retina

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2515-2522 ◽  
Author(s):  
M. Hojo ◽  
T. Ohtsuka ◽  
N. Hashimoto ◽  
G. Gradwohl ◽  
F. Guillemot ◽  
...  
Keyword(s):  
Glial Cell ◽  
Cell Fate ◽  
Glial Cells ◽  
Expression Patterns ◽  
Cell Number ◽  
Current Data ◽  
Mouse Retina ◽  
Cell Fate Specification ◽  
Bhlh Gene ◽  
Fate Specification

Neurons and glial cells differentiate from common precursors. Whereas the gene glial cells missing (gcm) determines the glial fate in Drosophila, current data about the expression patterns suggest that, in mammals, gcm homologues are unlikely to regulate gliogenesis. Here, we found that, in mouse retina, the bHLH gene Hes5 was specifically expressed by differentiating Muller glial cells and that misexpression of Hes5 with recombinant retrovirus significantly increased the population of glial cells at the expense of neurons. Conversely, Hes5-deficient retina showed 30–40% decrease of Muller glial cell number without affecting cell survival. These results indicate that Hes5 modulates glial cell fate specification in mouse retina.

scholarly journals Increased expression of Netrin-4 is associated with allodynia in a trigeminal neuropathic pain model rats by infraorbital nerve injury

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0251013
Author(s):  
Yuka Honjo ◽  
Yuki Fujita ◽  
Hitoshi Niwa ◽  
Toshihide Yamashita
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Infraorbital Nerve ◽  
Maxillofacial Region ◽  
Neuropathic Pain Model ◽  
Neurite Formation ◽  
Circuit Formation ◽  
Somatosensory Nervous System

Neuropathic pain refers to pain caused by lesions or diseases of the somatosensory nervous system that is characteristically different from nociceptive pain. Moreover, neuropathic pain occurs in the maxillofacial region due to various factors and is treated using tricyclic antidepressants and nerve block therapy; however, some cases do not fully recover. Netrin is a secreted protein crucially involved in neural circuit formation during development, including cell migration, cell death, neurite formation, and synapse formation. Recent studies show Netrin-4 expressed in the dorsal horn of the spinal cord is associated with chronic pain. Here we found involvement of Netrin-4 in neuropathic pain in the maxillofacial region. Netrin-4, along with one of its receptors, Unc5B, are expressed in the caudal subnucleus of the trigeminal spinal tract nucleus. Inhibition of its binding by anti-Netrin-4 antibodies not only shows a behavioral analgesic effect but also neuronal activity suppression. There was increased Netrin-4 expression at 14 days after infraorbital nerve injury. Our findings suggest that Netrin-4 induced by peripheral nerve injury causes neuropathic pain via Unc5B.

scholarly journals Filopodial dynamics and growth cone stabilization in Drosophila visual circuit development

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mehmet Neset Özel ◽  
Marion Langen ◽  
Bassem A Hassan ◽  
P Robin Hiesinger
Keyword(s):  
Growth Cone ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Stochastic Dynamics ◽  
Axon Growth ◽  
Growth Cones ◽  
Direct Role ◽  
Control Growth ◽  
Photoreceptor Neurons ◽  
Circuit Assembly

Filopodial dynamics are thought to control growth cone guidance, but the types and roles of growth cone dynamics underlying neural circuit assembly in a living brain are largely unknown. To address this issue, we have developed long-term, continuous, fast and high-resolution imaging of growth cone dynamics from axon growth to synapse formation in cultured Drosophila brains. Using R7 photoreceptor neurons as a model we show that >90% of the growth cone filopodia exhibit fast, stochastic dynamics that persist despite ongoing stepwise layer formation. Correspondingly, R7 growth cones stabilize early and change their final position by passive dislocation. N-Cadherin controls both fast filopodial dynamics and growth cone stabilization. Surprisingly, loss of N-Cadherin causes no primary targeting defects, but destabilizes R7 growth cones to jump between correct and incorrect layers. Hence, growth cone dynamics can influence wiring specificity without a direct role in target recognition and implement simple rules during circuit assembly.

scholarly journals LOTUS, an endogenous Nogo receptor antagonist, is involved in synapse and memory formation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryohei Nishida ◽  
Yuki Kawaguchi ◽  
Junpei Matsubayashi ◽  
Rie Ishikawa ◽  
Satoshi Kida ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Neural Circuit ◽  
Gene Knockout ◽  
Memory Function ◽  
Axon Growth ◽  
Memory Formation ◽  
Social Recognition ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Nogo Receptor

AbstractThe Nogo signal is involved in impairment of memory formation. We previously reported the lateral olfactory tract usher substance (LOTUS) as an endogenous antagonist of the Nogo receptor 1 that mediates the inhibition of axon growth and synapse formation. Moreover, we found that LOTUS plays an essential role in neural circuit formation and nerve regeneration. However, the effects of LOTUS on synapse formation and memory function have not been elucidated. Here, we clearly showed the involvement of LOTUS in synapse formation and memory function. The cultured hippocampal neurons derived from lotus gene knockout (LOTUS-KO) mice exhibited a decrease in synaptic density compared with those from wild-type mice. We also found decrease of dendritic spine formation in the adult hippocampus of LOTUS-KO mice. Finally, we demonstrated that LOTUS deficiency impairs memory formation in the social recognition test and the Morris water maze test, indicating that LOTUS is involved in functions of social and spatial learning and memory. These findings suggest that LOTUS affects synapse formation and memory function.

Cullin-5 plays multiple roles in cell fate specification and synapse formation duringDrosophila development

2005 ◽  
Vol 232 (3) ◽  
pp. 865-875 ◽  
Author(s):  
Champakali Ayyub ◽  
Anindya Sen ◽  
Foster Gonsalves ◽  
Kishan Badrinath ◽  
Poonam Bhandari ◽  
...  
Keyword(s):  
Cell Fate ◽  
Synapse Formation ◽  
Multiple Roles ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Cullin 5

scholarly journals Trans-Axonal Signaling in Neural Circuit Wiring

2020 ◽  
Vol 21 (14) ◽  
pp. 5170 ◽  
Author(s):  
Olivia Spead ◽  
Fabienne E. Poulain
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Target Selection ◽  
Synaptic Connectivity ◽  
Recent Advances ◽  
Complex Process ◽  
Circuit Formation

The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon–environment and axon–target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon–axon interactions during the different steps of neural circuit formation.

scholarly journals From whole organism to ultrastructure: progress in axonal imaging for decoding circuit development

Development ◽  
2021 ◽  
Vol 148 (18) ◽  
Author(s):  
Cory J. Weaver ◽  
Fabienne E. Poulain
Keyword(s):  
Neural Circuit ◽  
Super Resolution ◽  
Axon Growth ◽  
Light Sheet ◽  
Growth Cones ◽  
Novel Technologies ◽  
Future Technology ◽  
Axon Development ◽  
Circuit Formation ◽  
Super Resolution Microscopy

ABSTRACT Since the pioneering work of Ramón y Cajal, scientists have sought to unravel the complexities of axon development underlying neural circuit formation. Micrometer-scale axonal growth cones navigate to targets that are often centimeters away. To reach their targets, growth cones react to dynamic environmental cues that change in the order of seconds to days. Proper axon growth and guidance are essential to circuit formation, and progress in imaging has been integral to studying these processes. In particular, advances in high- and super-resolution microscopy provide the spatial and temporal resolution required for studying developing axons. In this Review, we describe how improved microscopy has revolutionized our understanding of axonal development. We discuss how novel technologies, specifically light-sheet and super-resolution microscopy, led to new discoveries at the cellular scale by imaging axon outgrowth and circuit wiring with extreme precision. We next examine how advanced microscopy broadened our understanding of the subcellular dynamics driving axon growth and guidance. We finally assess the current challenges that the field of axonal biology still faces for imaging axons, and examine how future technology could meet these needs.

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