The impact of Megf10/Drpr gain-of-function on muscle development in Drosophila

Isabelle Draper; Madhurima Saha; Hannah Stonebreaker; Robert N. Salomon; Bahar Matin; Peter B. Kang

doi:10.1002/1873-3468.13348

The impact of Megf10/Drpr gain-of-function on muscle development in Drosophila

Isabelle Draper, Madhurima Saha, Hannah Stonebreaker, Robert N. Salomon, Bahar Matin, Peter B. Kang

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Recessive mutations in multiple epidermal growth factor-like domains 10 (MEGF10) underlie a rare congenital muscle disease known as MEGF10 myopathy. MEGF10 and its Drosophila homolog Draper (Drpr) are transmembrane receptors expressed in muscle and glia. Drpr deficiency is known to result in muscle abnormalities in flies. In the current study, flies that ubiquitously overexpress Drpr, or mouse Megf10, display developmental arrest. The phenotype is reproduced with overexpression in muscle, but not in other tissues, and with overexpression during intermediate stages of myogenesis, but not in myoblasts. We find that tubular muscle subtypes are particularly sensitive to Megf10/Drpr overexpression. Complementary genetic analyses show that Megf10/Drpr and Notch may interact to regulate myogenesis. Our findings provide a basis for investigating MEGF10 in muscle development using Drosophila.

Original language	English (US)
Pages (from-to)	680-696
Number of pages	17
Journal	FEBS Letters
Volume	593
Issue number	7
DOIs	https://doi.org/10.1002/1873-3468.13348
State	Published - Apr 2019
Externally published	Yes

Bibliographical note

Funding Information:
We are particularly obliged to Mary Logan (OHSU) and Marc Freeman (OHSU) for their generous gift of the transgenic UAS-drpr-I, UAS-drpr-II, UAS-drpr-III, UAS-Megf10 and drpr null Drosophila lines used in these studies. We appreciate the thoughtful comments of Alan S. Kopin, as well as the expert technical assistance of Paul Spindler and Kelsey Bittner at the Department of Pathology and Laboratory Medicine, Tufts Medical Center. The genetic analyses were carried out with Gal4 driver stocks obtained from the Bloomington Drosophila Stock Center at Indiana University (NIH P40OD018537). FlyBase databases were utilized throughout the project to design experiments and interpret results. This work was supported in part by NIH R01NS080929.

Publisher Copyright:
© 2019 Federation of European Biochemical Societies

Keywords

Drosophila
Drpr
Megf10
MEGF10 myopathy
myogenesis

Publisher link

10.1002/1873-3468.13348

Find It

Find It at U of M Libraries

Cite this

@article{ceca674ea48b478ba13c28331e4b2d0c,

title = "The impact of Megf10/Drpr gain-of-function on muscle development in Drosophila",

abstract = "Recessive mutations in multiple epidermal growth factor-like domains 10 (MEGF10) underlie a rare congenital muscle disease known as MEGF10 myopathy. MEGF10 and its Drosophila homolog Draper (Drpr) are transmembrane receptors expressed in muscle and glia. Drpr deficiency is known to result in muscle abnormalities in flies. In the current study, flies that ubiquitously overexpress Drpr, or mouse Megf10, display developmental arrest. The phenotype is reproduced with overexpression in muscle, but not in other tissues, and with overexpression during intermediate stages of myogenesis, but not in myoblasts. We find that tubular muscle subtypes are particularly sensitive to Megf10/Drpr overexpression. Complementary genetic analyses show that Megf10/Drpr and Notch may interact to regulate myogenesis. Our findings provide a basis for investigating MEGF10 in muscle development using Drosophila.",

keywords = "Drosophila, Drpr, Megf10, MEGF10 myopathy, myogenesis",

author = "Isabelle Draper and Madhurima Saha and Hannah Stonebreaker and Salomon, {Robert N.} and Bahar Matin and Kang, {Peter B.}",

note = "Funding Information: We are particularly obliged to Mary Logan (OHSU) and Marc Freeman (OHSU) for their generous gift of the transgenic UAS-drpr-I, UAS-drpr-II, UAS-drpr-III, UAS-Megf10 and drpr null Drosophila lines used in these studies. We appreciate the thoughtful comments of Alan S. Kopin, as well as the expert technical assistance of Paul Spindler and Kelsey Bittner at the Department of Pathology and Laboratory Medicine, Tufts Medical Center. The genetic analyses were carried out with Gal4 driver stocks obtained from the Bloomington Drosophila Stock Center at Indiana University (NIH P40OD018537). FlyBase databases were utilized throughout the project to design experiments and interpret results. This work was supported in part by NIH R01NS080929. Publisher Copyright: {\textcopyright} 2019 Federation of European Biochemical Societies",

year = "2019",

month = apr,

doi = "10.1002/1873-3468.13348",

language = "English (US)",

volume = "593",

pages = "680--696",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "7",

}

TY - JOUR

T1 - The impact of Megf10/Drpr gain-of-function on muscle development in Drosophila

AU - Draper, Isabelle

AU - Saha, Madhurima

AU - Stonebreaker, Hannah

AU - Salomon, Robert N.

AU - Matin, Bahar

AU - Kang, Peter B.

N1 - Funding Information: We are particularly obliged to Mary Logan (OHSU) and Marc Freeman (OHSU) for their generous gift of the transgenic UAS-drpr-I, UAS-drpr-II, UAS-drpr-III, UAS-Megf10 and drpr null Drosophila lines used in these studies. We appreciate the thoughtful comments of Alan S. Kopin, as well as the expert technical assistance of Paul Spindler and Kelsey Bittner at the Department of Pathology and Laboratory Medicine, Tufts Medical Center. The genetic analyses were carried out with Gal4 driver stocks obtained from the Bloomington Drosophila Stock Center at Indiana University (NIH P40OD018537). FlyBase databases were utilized throughout the project to design experiments and interpret results. This work was supported in part by NIH R01NS080929. Publisher Copyright: © 2019 Federation of European Biochemical Societies

PY - 2019/4

Y1 - 2019/4

N2 - Recessive mutations in multiple epidermal growth factor-like domains 10 (MEGF10) underlie a rare congenital muscle disease known as MEGF10 myopathy. MEGF10 and its Drosophila homolog Draper (Drpr) are transmembrane receptors expressed in muscle and glia. Drpr deficiency is known to result in muscle abnormalities in flies. In the current study, flies that ubiquitously overexpress Drpr, or mouse Megf10, display developmental arrest. The phenotype is reproduced with overexpression in muscle, but not in other tissues, and with overexpression during intermediate stages of myogenesis, but not in myoblasts. We find that tubular muscle subtypes are particularly sensitive to Megf10/Drpr overexpression. Complementary genetic analyses show that Megf10/Drpr and Notch may interact to regulate myogenesis. Our findings provide a basis for investigating MEGF10 in muscle development using Drosophila.

AB - Recessive mutations in multiple epidermal growth factor-like domains 10 (MEGF10) underlie a rare congenital muscle disease known as MEGF10 myopathy. MEGF10 and its Drosophila homolog Draper (Drpr) are transmembrane receptors expressed in muscle and glia. Drpr deficiency is known to result in muscle abnormalities in flies. In the current study, flies that ubiquitously overexpress Drpr, or mouse Megf10, display developmental arrest. The phenotype is reproduced with overexpression in muscle, but not in other tissues, and with overexpression during intermediate stages of myogenesis, but not in myoblasts. We find that tubular muscle subtypes are particularly sensitive to Megf10/Drpr overexpression. Complementary genetic analyses show that Megf10/Drpr and Notch may interact to regulate myogenesis. Our findings provide a basis for investigating MEGF10 in muscle development using Drosophila.

KW - Drosophila

KW - Drpr

KW - Megf10

KW - MEGF10 myopathy

KW - myogenesis

UR - http://dx.doi.org/10.1002/1873-3468.13348

U2 - 10.1002/1873-3468.13348

DO - 10.1002/1873-3468.13348

M3 - Article

C2 - 30802937

SN - 0014-5793

VL - 593

SP - 680

EP - 696

JO - FEBS Letters

JF - FEBS Letters

IS - 7

ER -