NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA)...

Olles dieđut

Bibliográfalaš dieđut
Váldodahkkit: Tomlinson, R, Li, Z, Zhang, Q, Goh, B, Thorek, D, Rajbhandari, L, Brushart, T, Minichiello, L, Zhou, F, Venkatesan, A, Clemens, T
Materiálatiipa: Journal article
Almmustuhtton: Cell Press 2016
_version_ 1826304172871385088
author Tomlinson, R
Li, Z
Zhang, Q
Goh, B
Li, Z
Thorek, D
Rajbhandari, L
Brushart, T
Minichiello, L
Zhou, F
Venkatesan, A
Clemens, T
author_facet Tomlinson, R
Li, Z
Zhang, Q
Goh, B
Li, Z
Thorek, D
Rajbhandari, L
Brushart, T
Minichiello, L
Zhou, F
Venkatesan, A
Clemens, T
author_sort Tomlinson, R
collection OXFORD
description Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.
first_indexed 2024-03-07T06:13:46Z
format Journal article
id oxford-uuid:f068dbaa-00c9-410e-92f6-03a32522bbab
institution University of Oxford
last_indexed 2024-03-07T06:13:46Z
publishDate 2016
publisher Cell Press
record_format dspace
spelling oxford-uuid:f068dbaa-00c9-410e-92f6-03a32522bbab2022-03-27T11:47:41ZNGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral BoneJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f068dbaa-00c9-410e-92f6-03a32522bbabSymplectic Elements at OxfordCell Press2016Tomlinson, RLi, ZZhang, QGoh, BLi, ZThorek, DRajbhandari, LBrushart, TMinichiello, LZhou, FVenkatesan, AClemens, TDeveloping tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.
spellingShingle Tomlinson, R
Li, Z
Zhang, Q
Goh, B
Li, Z
Thorek, D
Rajbhandari, L
Brushart, T
Minichiello, L
Zhou, F
Venkatesan, A
Clemens, T
NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_full NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_fullStr NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_full_unstemmed NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_short NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_sort ngf trka signaling by sensory nerves coordinates the vascularization and ossification of developing endochondral bone
work_keys_str_mv AT tomlinsonr ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT liz ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT zhangq ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT gohb ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT liz ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT thorekd ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT rajbhandaril ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT brushartt ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT minichiellol ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT zhouf ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT venkatesana ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone
AT clemenst ngftrkasignalingbysensorynervescoordinatesthevascularizationandossificationofdevelopingendochondralbone