Regulation of chemosensory and GABAergic motor neuron development by the C. elegans Aristaless/Arx homolog alr-1

Formation of the nervous system requires a complex series of events including proper extension and guidance of neuronal axons and dendrites. Here we investigate the requirement for integrins, a class of transmembrane cell adhesion receptors, in regulating these processes across classes of C. elegans motor neurons. We show α integrin/ina-1 is expressed by both GABAergic and cholinergic motor neurons. Despite this, our analysis of hypomorphic ina-1(gm144) mutants indicates preferential involvement of α integrin/ina-1 in GABAergic commissural development, without obvious involvement in cholinergic commissural development. The defects in GABAergic commissures of ina-1(gm144) mutants included both premature termination and guidance errors and were reversed by expression of wild type ina-1 under control of the native ina-1 promoter. Our results also show that α integrin/ina-1 is important for proper outgrowth and guidance of commissures from both embryonic and post-embryonic born GABAergic motor neurons, indicating an ongoing requirement for integrin through two phases of GABAergic neuron development. Our findings provide insights into neuron-specific roles for integrin that would not be predicted based solely upon expression analysis.

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An ancient role for Collier/Olf/Ebf (COE)-type transcription factors in axial motor neuron development

10.1101/454926 ◽

2018 ◽

Author(s):

Catarina Catela ◽

Edgar Correa ◽

Jihad Aburas ◽

Laura Croci ◽

G. Giacomo Consalez ◽

...

Keyword(s):

Transcription Factors ◽

Motor Neuron ◽

Molecular Mechanisms ◽

Neuron Development ◽

Spinal Alignment ◽

Knock Out ◽

Transgenic Expression ◽

C Elegans ◽

Functional Conservation ◽

Motor Circuits

ABSTRACTBackgroundMammalian motor circuits display remarkable cellular diversity with hundreds of motor neuron (MN) subtypes innervating hundreds of different muscles. Extensive research on limb muscle-innervating MNs has begun to elucidate the genetic programs that control animal locomotion. In striking contrast, the molecular mechanisms underlying the development of axial muscle-innervating MNs, which control breathing and spinal alignment, are poorly studied.MethodsOur previous studies indicated that the function of the Collier/Olf/Ebf (COE) family of transcription factors (TFs) in axial MN development may be conserved from nematodes to simple chordates. Here, we examine the expression pattern of all four mouse COE family members (mEbf1-mEbf4) in spinal MNs and employ genetic approaches in both nematodes and mice to investigate their function in axial MN development.ResultsWe report that mEbf1 and mEbf2 are expressed in distinct MN clusters (termed “columns”) that innervate different axial muscles. Mouse Ebf1 is expressed in MNs of the hypaxial motor column (HMC), which is necessary for breathing, while mEbf2 is expressed in MNs of the medial motor column (MMC) that control spinal alignment. Our characterization of Ebf2 knock-out mice revealed a requirement for Ebf2 in the differentiation of a subset of MMC MNs, indicating molecular diversity within MMC neurons. Intriguingly, transgenic expression of mEbf1 or mEbf2 can rescue axial MN differentiation and locomotory defects in nematodes (Caenorhabditis elegans) lacking unc-3, the sole C. elegans ortholog of the COE family, suggesting functional conservation among mEbf1, mEbf2 and nematode UNC-3.ConclusionsThese findings support the hypothesis that the genetic programs controlling axial MN development are deeply conserved across species, and further advance our understanding of such programs by revealing an essential role for Ebf2 in mouse axial MNs. Because human mutations in COE ortholgs lead to neurodevelopmental disorders characterized by motor developmental delay, our findings may advance our understanding of these human conditions.

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Diversification of C. elegans Motor Neuron Identity via Selective Effector Gene Repression

Neuron ◽

10.1016/j.neuron.2016.11.036 ◽

2017 ◽

Vol 93 (1) ◽

pp. 80-98 ◽

Cited By ~ 29

Author(s):

Sze Yen Kerk ◽

Paschalis Kratsios ◽

Michael Hart ◽

Romulo Mourao ◽

Oliver Hobert

Keyword(s):

Motor Neuron ◽

Gene Repression ◽

C Elegans ◽

Effector Gene

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The C. elegans NeuroD homolog cnd-1 functions in multiple aspects of motor neuron fate specification

Development ◽

10.1242/dev.127.19.4239 ◽

2000 ◽

Vol 127 (19) ◽

pp. 4239-4252 ◽

Cited By ~ 2

Author(s):

S. Hallam ◽

E. Singer ◽

D. Waring ◽

Y. Jin

Keyword(s):

Motor Neuron ◽

Motor Neurons ◽

Expression Patterns ◽

Loss Of Function ◽

Variable Expression ◽

C Elegans ◽

Helix Loop Helix ◽

Ventral Cord ◽

Bhlh Proteins ◽

Neuronal Type

The basic helix-loop-helix transcription factor NeuroD (Neurod1) has been implicated in neuronal fate determination, differentiation and survival. Here we report the expression and functional analysis of cnd-1, a C. elegans NeuroD homolog. cnd-1 expression was first detected in neuroblasts of the AB lineage in 14 cell embryos and maintained in many neuronal descendants of the AB lineage during embryogenesis, diminishing in most terminally differentiated neurons prior to hatching. Specifically, cnd-1 reporter genes were expressed in the precursors of the embryonic ventral cord motor neurons and their progeny. A loss-of-function mutant, cnd-1(ju29), exhibited multiple defects in the ventral cord motor neurons. First, the number of motor neurons was reduced, possibly caused by the premature withdrawal of the precursors from mitotic cycles. Second, the strict correlation between the fate of a motor neuron with respect to its lineage and position in the ventral cord was disrupted, as manifested by the variable expression pattern of motor neuron fate specific markers. Third, motor neurons also exhibited defects in terminal differentiation characteristics including axonal morphology and synaptic connectivity. Finally, the expression patterns of three neuronal type-specific transcription factors, unc-3, unc-4 and unc-30, were altered. Our data suggest that cnd-1 may specify the identity of ventral cord motor neurons both by maintaining the mitotic competence of their precursors and by modulating the expression of neuronal type-specific determination factors. cnd-1 appears to have combined the functions of several vertebrate neurogenic bHLH proteins and may represent an ancestral form of this protein family.

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lncrps25 play an essential role in motor neuron development through controlling the expression of olig2 in zebrafish

Journal of Cellular Physiology ◽

10.1002/jcp.29237 ◽

2019 ◽

Vol 235 (4) ◽

pp. 3485-3496 ◽

Cited By ~ 3

Author(s):

Tianheng Gao ◽

Jingyun Li ◽

Nan Li ◽

Yan Gao ◽

Lingling Yu ◽

...

Keyword(s):

Motor Neuron ◽

Essential Role ◽

Neuron Development

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MiR-375 is Essential for Human Spinal Motor Neuron Development and May Be Involved in Motor Neuron Degeneration

Stem Cells ◽

10.1002/stem.2233 ◽

2015 ◽

Vol 34 (1) ◽

pp. 124-134 ◽

Cited By ~ 35

Author(s):

Akshay Bhinge ◽

Seema C. Namboori ◽

Angela Bithell ◽

Chiara Soldati ◽

Noel J. Buckley ◽

...

Keyword(s):

Motor Neuron ◽

Neuron Development ◽

Motor Neuron Degeneration ◽

Neuron Degeneration ◽

Spinal Motor Neuron ◽

Spinal Motor

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Insm1a Regulates Motor Neuron Development in Zebrafish

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2017.00274 ◽

2017 ◽

Vol 10 ◽

Cited By ~ 15

Author(s):

Jie Gong ◽

Xin Wang ◽

Chenwen Zhu ◽

Xiaohua Dong ◽

Qinxin Zhang ◽

...

Keyword(s):

Motor Neuron ◽

Neuron Development

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Effects of metal exposure on motor neuron development, neuromasts and the escape response of zebrafish embryos

Neurotoxicology and Teratology ◽

10.1016/j.ntt.2015.05.006 ◽

2015 ◽

Vol 50 ◽

pp. 33-42 ◽

Cited By ~ 27

Author(s):

Laura Sonnack ◽

Sebastian Kampe ◽

Elke Muth-Köhne ◽

Lothar Erdinger ◽

Nicole Henny ◽

...

Keyword(s):

Motor Neuron ◽

Escape Response ◽

Metal Exposure ◽

Zebrafish Embryos ◽

Neuron Development

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Isl1 Is required for multiple aspects of motor neuron development

Molecular and Cellular Neuroscience ◽

10.1016/j.mcn.2011.04.007 ◽

2011 ◽

Vol 47 (3) ◽

pp. 215-222 ◽

Cited By ~ 47

Author(s):

Xingqun Liang ◽

Mi-Ryoung Song ◽

ZengGuang Xu ◽

Guillermo M. Lanuza ◽

Yali Liu ◽

...

Keyword(s):

Motor Neuron ◽

Neuron Development

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Groucho/TLE opposes axial to hypaxial motor neuron development

10.1101/2020.03.10.986323 ◽

2020 ◽

Author(s):

Adèle Salin-Cantegrel ◽

Rola Dali ◽

Jae Woong Wang ◽

Marielle Beaulieu ◽

Mira Deshmukh ◽

...

Keyword(s):

Spinal Cord ◽

Motor Neuron ◽

Motor Neurons ◽

Molecular Mechanisms ◽

List Type ◽

Neuron Development ◽

In Ovo ◽

Motor Circuits ◽

Axial Muscles ◽

Muscle Innervation

ABSTRACTSpinal cord motor neuron diversity and the ensuing variety of motor circuits allow for the processing of elaborate muscular behaviours such as body posture and breathing. Little is known, however, about the molecular mechanisms behind the specification of axial and hypaxial motor neurons controlling postural and respiratory functions respectively. Here we show that the Groucho/TLE (TLE) transcriptional corepressor is a multi-step regulator of axial and hypaxial motor neuron diversification in the developing spinal cord. TLE first promotes axial motor neuron specification at the expense of hypaxial identity by cooperating with non-canonical WNT5A signalling within the motor neuron progenitor domain. TLE further acts during post-mitotic motor neuron diversification to promote axial motor neuron topology and axonal connectivity whilst suppressing hypaxial traits. These findings provide evidence for essential and sequential roles of TLE in the spatial and temporal coordination of events regulating the development of motor neurons influencing posture and controlling respiration.HIGHLIGHTSGroucho/TLE mediates non-canonical WNT signalling in developing motor neuronsNon canonical WNT:TLE pathway regulates thoracic motor neuron diversificationTLE promotes axial while inhibiting hypaxial motor neuron developmentTLE influences developing motor neuron topology and muscle innervationIN BRIEFSalin-Cantegrel et al use in ovo engineered approaches to show that a non-canonical WNT:TLE pathway coordinates temporally and spatially separated elements of motor neuron diversification, repressing hypaxial motor neuron development to promote the axial fate.GRAPHICAL ABSTRACTTLE contribution to the development of thoracic somatic motor columnsProgenitor cells in the ventral pMN domain are exposed to higher concentrations of non-canonical WNTs and express more TLE. Cooperation of non-canonical WNTs and TLE renders ventral pMN progenitors refractory to a respiratory MN fate, thereby contributing to the separation of MMC and RMC MN lineages. Differentiating MNs that maintain high TLE expression also maintain LHX3 expression, adopt axial motor neuron topology and connect to axial muscles. TLE activity in differentiating MMC MNs prevents the acquisition of respiratory MN topology and innervation traits.

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