Mutations in the Notch Pathway Alter the Patterning of Multifidus

Fisher, Rebecca E.; Smith, Heather F.; Kusumi, Kenro; Tassone, Erica E.; Rawls, Alan; Wilson‐Rawls, Jeanne

doi:10.1002/ar.21488

Cited by 5 publications

(2 citation statements)

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“…While combinatorial expression of Islet1, Islet2, Lhx3 and Hb9 demarcates MMC columnar identity [1, 6], molecular markers that label subsets of MMC neurons have not been identified in mice. Since MMC neurons innervate different types of epaxial muscle, such as spinalis, longissimus, and iliocostalis [11], is this anatomical diversity accompanied by molecular diversity?…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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BackgroundMammalian 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 uncovered a requirement for Ebf2 in the differentiation program of a subset of MMC MNs and revealed for the first time 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 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 orthologs lead to neurodevelopmental disorders characterized by motor developmental delay, our findings may advance our understanding of these human conditions.Electronic supplementary materialThe online version of this article (10.1186/s13064-018-0125-6) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Because of the important association between scoliosis and paravertebral muscle imbalance, numerous studies have evaluated biopsies of the spinal rotator muscles for potential changes that may elucidate the etiology of AIS [ 5 , 16 – 23 ]. Here we describe two patients with clinical and radiological findings of AIS who were operated on and subjected to multifidus muscle biopsy, which demonstrated anatomopathological results suggestive of core myopathy.…”

Section: Introductionmentioning

confidence: 99%

Adolescent idiopathic scoliosis without limb weakness: a differential diagnosis of core myopathy?

Luciano

Puertas

Martins

et al. 2015

BMC Musculoskelet Disord

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BackgroundCore myopathies are a clinically and genetically heterogeneous group of congenital myopathies with the common defined histopathological feature of focally reduced oxidative activity on muscle biopsy. It has a low incidence, however, recent articles show broad clinical spectrum, suggesting that the real incidence should be considerably larger than previously described. Due to the important association between scoliosis and paravertebral muscle imbalance, numerous authors study, by biopsy of the spinal rotator muscles, potential changes that may elucidate the etiology of adolescent idiopathic scoliosis.Case presentationTwo patients have been followed at Spine Group of Department of Orthopedics at Federal University of São Paulo, with an initial diagnosis of idiopathic scoliosis. Both patients had clinical and radiological findings compatible with it. The patients authorized, through the Term of Consent, intraoperative biopsy of muscle multifidus from the apex of the thoracic curve on concave and convex sides. After muscle biopsy was performed a histopathological analysis. As regard to the histopathological features: in both patients were identified, the presence of core structures in extensive areas with reduced oxidative activity running along the muscle fiber.ConclusionsAll patients with ‘idiopathic’ scoliosis deserve a careful neurological evaluation, even if they have minimal muscle symptoms in the extremities. The frequent occurrence of scoliosis in patients with CORE Myopathies, supports the thesis that the change in the paravertebral muscle fiber must be the underlying pathogenic factor in scoliosis and may help us understand the onset and progression of curves in patients previously diagnosed with idiopathic scoliosis.

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Developmental and Functional Anatomy of the Spine

Rawls¹,

Fisher²

2018

The Genetics and Development of Scoliosis

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Mutations in the Notch Pathway Alter the Patterning of Multifidus

Cited by 5 publications

References 74 publications

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

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

Adolescent idiopathic scoliosis without limb weakness: a differential diagnosis of core myopathy?

Developmental and Functional Anatomy of the Spine

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