Mice deficient in the chemokine receptor CXCR4 exhibit impaired limb innervation and myogenesis

Veysel Odemis; Elke Lamp; Gita Pezeshki; Barbara Moepps; Karl Schilling; Peter Gierschik; Dan R Littman; Jürgen Engele

doi:10.1016/j.mcn.2005.07.019

Mice deficient in the chemokine receptor CXCR4 exhibit impaired limb innervation and myogenesis

Mol Cell Neurosci. 2005 Dec;30(4):494-505. doi: 10.1016/j.mcn.2005.07.019. Epub 2005 Sep 29.

Authors

Veysel Odemis¹, Elke Lamp, Gita Pezeshki, Barbara Moepps, Karl Schilling, Peter Gierschik, Dan R Littman, Jürgen Engele

Affiliation

¹ Institute of Anatomy, University of Leipzig, Medical Faculty, Liebigstr. 13, 04103 Leipzig, Germany.

PMID: 16198599
DOI: 10.1016/j.mcn.2005.07.019

Abstract

The chemokine CXCL12/SDF-1 and its receptor CXCR4 regulate the development and the function of the hematopoietic system and control morphogenesis of distinct brain areas. Here, we demonstrate that inactivation of CXCR4 results in a massive loss of spinal cord motoneurons and dorsal root ganglion neurons and, subsequently, in a reduced innervation of the developing mouse fore- and hindlimbs. However, only the death of sensory neurons seems to be a direct consequence of receptor inactivation as suggested by the observations that DRG neurons, but not motoneurons, of wild-type animals express CXCR4 and respond to CXCL12 with an increase in cell survival. In contrast, the increased death of motoneurons in CXCR4-deficient animals seems to result from impaired limb myogenesis and a subsequent loss of muscle-derived neurotrophic support. In summary, our findings unravel a previously unrecognized complex role of CXCL12/CXCR4 in the control of limb neuromuscular development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Death / drug effects
Cell Death / genetics
Chemokine CXCL12
Chemokines, CXC / metabolism
Chemokines, CXC / pharmacology
Extremities
Female
Ganglia, Spinal / abnormalities
Ganglia, Spinal / pathology
Ganglia, Spinal / physiopathology
Limb Deformities, Congenital / genetics*
Limb Deformities, Congenital / immunology
Limb Deformities, Congenital / metabolism
Male
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Motor Neurons / metabolism
Motor Neurons / pathology
Motor Neurons / ultrastructure
Muscle, Skeletal / abnormalities*
Muscle, Skeletal / innervation*
Muscle, Skeletal / physiopathology
Nerve Growth Factors / deficiency
Neurons, Afferent / metabolism
Neurons, Afferent / pathology
Neurons, Afferent / ultrastructure
Peripheral Nerves / abnormalities*
Peripheral Nerves / pathology
Peripheral Nerves / physiopathology
Receptors, CXCR4 / genetics*
Spinal Cord / abnormalities*
Spinal Cord / pathology
Spinal Cord / physiopathology

Substances

Chemokine CXCL12
Chemokines, CXC
Cxcl12 protein, mouse
Nerve Growth Factors
Receptors, CXCR4