A Cxcl12-Cxcr4 Chemokine Signaling Pathway Defines the Initial Trajectory of Mammalian Motor Axons

Lieberam, Ivo; Agalliu, Dritan; Nagasawa, Takashi; Ericson, Johan; Jessell, Thomas M.

doi:10.1016/j.neuron.2005.08.011

Cited by 162 publications

(170 citation statements)

References 56 publications

Supporting

Mentioning

160

Contrasting

Order By: Relevance

“…Indeed, it is clear that the chemokine SDF-1 and its receptor CXCR4 play an important role in the development of the nervous system and other tissues. In the nervous system, SDF-1/CXCR4 signaling directs the migration of neural stem cells to a number of different parts of the brain (Zou et al, 1998;Bagri et al, 2002;Lu et al, 2002;Stumm et al, 2003) and the DRG (Belmadani et al, 2005) and also plays a role as an axonal guidance cue (Xiang et al, 2002;Arakawa et al, 2003;Chalasani et al, 2003;Lieberam et al, 2005;Pujol et al, 2005). It has also been demonstrated that neurospheres prepared from postnatal brains express CXCR4 as well as other chemokine receptors (Lazarini et al, 2000;Stumm et al, 2003;Ji et al, 2004;Peng et al, 2004;Tran et al, 2004) and that chemokines act as chemoattractants for these cells (Pluchino et al, 2005;Tran et al, 2004Tran et al, , 2005Widera et al, 2004), suggesting that chemokine-mediated effects may also be important in the regulation of adult progenitor cell migration.…”

Section: Discussionmentioning

confidence: 99%

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

Tran

Banisadr

Ren

et al. 2006

J of Comparative Neurology

219

228

View full text Add to dashboard Cite

We previously demonstrated that chemokine receptors are expressed by neural progenitors grown as cultured neurospheres. To examine the significance of these findings for neural progenitor function in vivo, we investigated whether chemokine receptors were expressed by cells having the characteristics of neural progenitors in neurogenic regions of the postnatal brain. Using in situ hybridization we demonstrated the expression of CCR1, CCR2, CCR5, CXCR3, and CXCR4 chemokine receptors by cells in the dentate gyrus (DG), subventricular zone of the lateral ventricle, and olfactory bulb. The pattern of expression for all of these receptors was similar, including regions where neural progenitors normally reside. In addition, we attempted to colocalize chemokine receptors with markers for neural progenitors. In order to do this we used nestin-EGFP and TLXLacZ transgenic mice, as well as labeling for Ki67, a marker for dividing cells. In all three areas of the brain we demonstrated colocalization of chemokine receptors with these three markers in populations of cells. Expression of chemokine receptors by neural progenitors was further confirmed using CXCR4-EGFP BAC transgenic mice. Expression of CXCR4 in the DG included cells that expressed nestin and GFAP as well as cells that appeared to be immature granule neurons expressing PSA-NCAM, calretinin, and Prox-1. CXCR4-expressing cells in the DG were found in close proximity to immature granule neurons that expressed the chemokine SDF-1/CXCL12. Cells expressing CXCR4 frequently coexpressed CCR2 receptors. These data support the hypothesis that chemokine receptors are important in regulating the migration of progenitor cells in postnatal brain. Indexing terms stem cells; development; chemotaxis; brain repairDuring embryogenesis, neural stem/progenitor cells must migrate long distances from the germinal epithelia where they are born to their final destinations (Hatten, 1999;Alvarez-Buylla et al., 2001). During migration, stem cells may continue to divide and also become restricted in terms of their ultimate phenotypes. Thus, the timing of neuro-and gliogenesis in the developing embryo is precisely controlled (Rallu et al., 2002). The factors that determine the migration, proliferation, and differentiation of embryonic stem cells have been widely investigated and numerous factors have been shown to influence these processes (Lindvall et al., 2004). One group of molecules that has recently been shown to control progenitor cell migration in the nervous system are the chemokines (CHEMO-tactic cytoKINES) (Tran and © NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript Miller, 2003). The chemokines are a family of small secreted proteins that are known to be important regulators of leukocyte trafficking under both normal conditions and during inflammatory responses (Moser et al., 2004). Furthermore, it is now known that chemokine signaling has an important role to play in the developing embryo. Deletion of the genes for the CXCR4 chemokine receptor or f...

show abstract

Section: Discussionmentioning

confidence: 99%

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

Tran

Banisadr

Ren

et al. 2006

J of Comparative Neurology

219

228

View full text Add to dashboard Cite

show abstract

“…To our surprise, Shh signaling appeared normal in 26-1 mutants, but motor axons projected their axons dorsally rather than ventrally. At present, only two genes, the chemokine stromal cell-derived factor 1 (SDF1) (Cxcl12) and its receptor Cxcr4, have been shown to have specific roles in governing initial ventrally directed motor axon outgrowth (Lieberam et al, 2005). The 26-1 mutation is in neither of these genes.…”

Section: Discussionmentioning

confidence: 99%

A Genetic Screen for Mutations That Affect Cranial Nerve Development in the Mouse

Mar

Rivkin²,

Kim³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

Cranial motor and sensory nerves arise stereotypically in the embryonic hindbrain, act as sensitive indicators of general and regionspecific neuronal development, and are directly or indirectly affected in many human disorders, particularly craniofacial syndromes. The molecular genetic hierarchies that regulate cranial nerve development are mostly unknown. Here, we describe the first mouse genetic screen that has used direct immunohistochemical visualization methods to systematically identify genetic loci required for cranial nerve development. After screening 40 pedigrees, we recovered seven new neurodevelopmental mutations. Two mutations model human genetic syndromes. Mutation 7-1 causes facial nerve anomalies and a reduced lower jaw, and is located in a region of conserved synteny with an interval associated with the micrognathia and mental retardation of human cri-du-chat syndrome. Mutation 22-1 is in the Pax3 gene and, thus, models human Waardenburg syndrome. Three mutations cause global axon guidance deficits: one interferes with initial motor axon extension from the neural tube, another causes overall axon defasciculation, and the third affects general choice point selection. Another two mutations affect the oculomotor nerve specifically. Oculomotor nerve development, which is disrupted by six mutations, appears particularly sensitive to genetic perturbations. Phenotypic comparisons of these mutants identifies a "transition zone" that oculomotor axons enter after initial outgrowth and in which new factors govern additional progress. The number of interesting neurodevelopmental mutants revealed by this small-scale screen underscores the promise of similar focused genetic screens to contribute significantly to our understanding of cranial nerve development and human craniofacial syndromes.

show abstract

“…The immune system modulates cellular events across different phases of the normal brain development (Boulanger, 2009;Deverman and Patterson, 2009), and here we give an overview of key immune influences on postnatal cellular events. With regard to synaptogenesis, the chemokine CXCL12 and its receptor CXCR4 regulate axonal elongation, branching, and pathfinding by modulating neuronal responses to axon guidance cues (eg, Slit-2, semaphorin 3A, and semaphorin 3C; Chalasani et al, 2003;Tran and Miller, 2003), and CXCR4 and CXCL12 mutant mice show disrupted axonal migration (Lieberam et al, 2005). With regard to synaptic refinement, the immune system modulates the strength of neuronal excitatory synapses to stabilize firing in the context of varying neuronal activity (ie, synaptic scaling).…”

Section: Early-life Immune Activation and Brain Developmentmentioning

confidence: 99%

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

Danese

Lewis

2016

Neuropsychopharmacol

294

191

View full text Add to dashboard Cite

The brain and the immune system are not fully formed at birth, but rather continue to mature in response to the postnatal environment. The two-way interaction between the brain and the immune system makes it possible for childhood psychosocial stressors to affect immune system development, which in turn can affect brain development and its long-term functioning. Drawing from experimental animal models and observational human studies, we propose that the psychoneuroimmunology of early-life stress can offer an innovative framework to understand and treat psychopathology linked to childhood trauma. Earlylife stress predicts later inflammation, and there are striking analogies between the neurobiological correlates of early-life stress and of inflammation. Furthermore, there are overlapping trans-diagnostic patterns of association of childhood trauma and inflammation with clinical outcomes. These findings suggest new strategies to remediate the effect of childhood trauma before the onset of clinical symptoms, such as anti-inflammatory interventions and potentiation of adaptive immunity. Similar strategies might be used to ameliorate the unfavorable treatment response described in psychiatric patients with a history of childhood trauma.

show abstract

A Cxcl12-Cxcr4 Chemokine Signaling Pathway Defines the Initial Trajectory of Mammalian Motor Axons

Cited by 162 publications

References 56 publications

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

A Genetic Screen for Mutations That Affect Cranial Nerve Development in the Mouse

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

Contact Info

Product

Resources

About