Knockdown of Slit signalling during limb development leads to a reduction in humerus length

Alexandra Rafipay; Xin-Peng  Dun; David B  Parkinson; Lynda Erskine; Neil Vargesson

doi:10.1002/dvdy.284

Knockdown of Slit signalling during limb development leads to a reduction in humerus length

Alexandra Rafipay, Xin-Peng Dun, David B Parkinson, Lynda Erskine, Neil Vargesson^* (Corresponding Author)

^*Corresponding author for this work

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

5 Citations (Scopus)

1 Downloads (Pure)

Abstract

BACKGROUND: Slits (1-3) and their Robo (1-3) receptors play multiple non-neuronal roles in development, including in development of muscle, heart and mammary gland. Previous work has demonstrated expression of Slit and Robo family members during limb development, where their functions are unclear.

RESULTS: In situ hybridisation confirmed strong expression of Slit2, Slit3, Robo1, and Robo2 throughout mouse limb and joint development. No expression of Slit1 or Robo3 was detected. Analysis of Slit1/2 or Slit3 knockout mice revealed normal limb development. In contrast, locally blocking Slit signalling though grafting of cells expressing a dominant-negative Robo2 construct in the proximo-central region of developing chicken limb buds caused significant shortening of the humerus.

CONCLUSIONS: These findings demonstrate an essential role for Slit/Robo signalling in regulating bone length during chicken limb development. This article is protected by copyright. All rights reserved.

Original language	English
Pages (from-to)	1340-1357
Number of pages	18
Journal	Developmental Dynamics
Volume	250
Issue number	9
Early online date	21 Dec 2020
DOIs	https://doi.org/10.1002/dvdy.284
Publication status	Published - 1 Sep 2021

Keywords

Robo
Slit
Mouse
Mouse knockout
chicken
Hinnlimb
Gene expression
bone development

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Rafipay_et_al_DD_KnockdownOfSlitSignalling_AAM
This is the peer reviewed version of the following article: Rafipay, A, Dun, X-P, Parkinson, DB, Erskine, L, Vargesson, N. Knockdown of slit signaling during limb development leads to a reduction in humerus length. Developmental Dynamics. 2021; 250: 1340– 1357. , which has been published in final form at https://doi.org/10.1002/dvdy.284. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Accepted author manuscript, 4.48 MBLicence: Unspecified

Cite this

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title = "Knockdown of Slit signalling during limb development leads to a reduction in humerus length",

abstract = "BACKGROUND: Slits (1-3) and their Robo (1-3) receptors play multiple non-neuronal roles in development, including in development of muscle, heart and mammary gland. Previous work has demonstrated expression of Slit and Robo family members during limb development, where their functions are unclear.RESULTS: In situ hybridisation confirmed strong expression of Slit2, Slit3, Robo1, and Robo2 throughout mouse limb and joint development. No expression of Slit1 or Robo3 was detected. Analysis of Slit1/2 or Slit3 knockout mice revealed normal limb development. In contrast, locally blocking Slit signalling though grafting of cells expressing a dominant-negative Robo2 construct in the proximo-central region of developing chicken limb buds caused significant shortening of the humerus.CONCLUSIONS: These findings demonstrate an essential role for Slit/Robo signalling in regulating bone length during chicken limb development. This article is protected by copyright. All rights reserved.",

keywords = "Robo, Slit, Mouse, Mouse knockout, chicken, Hinnlimb, Gene expression, bone development",

author = "Alexandra Rafipay and Xin-Peng Dun and Parkinson, {David B} and Lynda Erskine and Neil Vargesson",

note = "Acknowledgements: This project was funded by an EastBio BBSRC DTP PhD Studentship to AR. The authors thank past and present lab staff for helpful discussions.",

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doi = "10.1002/dvdy.284",

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T1 - Knockdown of Slit signalling during limb development leads to a reduction in humerus length

AU - Rafipay, Alexandra

AU - Dun, Xin-Peng

AU - Parkinson, David B

AU - Erskine, Lynda

AU - Vargesson, Neil

N1 - Acknowledgements: This project was funded by an EastBio BBSRC DTP PhD Studentship to AR. The authors thank past and present lab staff for helpful discussions.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - BACKGROUND: Slits (1-3) and their Robo (1-3) receptors play multiple non-neuronal roles in development, including in development of muscle, heart and mammary gland. Previous work has demonstrated expression of Slit and Robo family members during limb development, where their functions are unclear.RESULTS: In situ hybridisation confirmed strong expression of Slit2, Slit3, Robo1, and Robo2 throughout mouse limb and joint development. No expression of Slit1 or Robo3 was detected. Analysis of Slit1/2 or Slit3 knockout mice revealed normal limb development. In contrast, locally blocking Slit signalling though grafting of cells expressing a dominant-negative Robo2 construct in the proximo-central region of developing chicken limb buds caused significant shortening of the humerus.CONCLUSIONS: These findings demonstrate an essential role for Slit/Robo signalling in regulating bone length during chicken limb development. This article is protected by copyright. All rights reserved.

AB - BACKGROUND: Slits (1-3) and their Robo (1-3) receptors play multiple non-neuronal roles in development, including in development of muscle, heart and mammary gland. Previous work has demonstrated expression of Slit and Robo family members during limb development, where their functions are unclear.RESULTS: In situ hybridisation confirmed strong expression of Slit2, Slit3, Robo1, and Robo2 throughout mouse limb and joint development. No expression of Slit1 or Robo3 was detected. Analysis of Slit1/2 or Slit3 knockout mice revealed normal limb development. In contrast, locally blocking Slit signalling though grafting of cells expressing a dominant-negative Robo2 construct in the proximo-central region of developing chicken limb buds caused significant shortening of the humerus.CONCLUSIONS: These findings demonstrate an essential role for Slit/Robo signalling in regulating bone length during chicken limb development. This article is protected by copyright. All rights reserved.

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KW - Slit

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KW - Mouse knockout

KW - chicken

KW - Hinnlimb

KW - Gene expression

KW - bone development

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DO - 10.1002/dvdy.284

M3 - Article

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VL - 250

SP - 1340

EP - 1357

JO - Developmental Dynamics

JF - Developmental Dynamics

SN - 1058-8388

IS - 9

ER -

Knockdown of Slit signalling during limb development leads to a reduction in humerus length

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