Developmental pattern of expression of the alpha chemokine stromal cell‐derived factor 1 in the rat central nervous system

Abstract

Stromal cell-derived factor 1 (SDF-1) is an alpha-chemokine that stimulates migration of haematopoietic progenitor cells and development of the immune system. SDF-1 is also abundantly and selectively expressed in the developing and mature CNS, as we show here. At embryonic day 15, SDF-1 transcripts were detected in the germinal periventricular zone and in the deep layer of the forming cerebral cortex. At birth, granule cells in the cerebellum and glial cells of the olfactory bulb outer layer showed an SDF-1 in situ hybridization signal that decreased progressively within the next 2 weeks. In other regions such as cortex, thalamus and hippocampus, SDF-1 transcripts detected at birth progressively increased in abundance during the postnatal period. SDF-1 protein was identified by immunoblot and/or immunocytochemistry in most brain regions where these transcripts were detected. SDF-1 was selectively localized in some thalamic nuclei and neurons of the fifth cortical layer as well as in pontine and brainstem nuclei which relay the nociceptive response. The presence of SDF-1 transcripts in cerebellar granule cells was correlated with their migration from the external to the inner granular layers with disappearance of the signal when migration was completed. In contrast, SDF1 mRNA signal increased during formation of the hippocampal dentate gyrus and stayed high in this region throughout life. The selective and regulated expression of SDF-1 in these regions suggests a role in precursor migration, neurogenesis and, possibly, synaptogenesis. Thus this alpha chemokine may be as essential to nervous system function as it is to the immune system.

SDF1α/CXCR4 Signaling, via ERKs and the Transcription Factor Egr1, Induces Expression of a 67-kDa Form of Glutamic Acid Decarboxylase in Embryonic Hippocampal Neurons

“…Our data demonstrate that activation of the SDF1␣-CXCR4 signaling pathway up-regulates the expression of GAD67 and the production of GABA in embryonic hippocampal neurons. In the developing hippocampus SDF1␣ may play an important role in regulating neurogenesis, gliogenesis, and the migration of dentate granule cells and synaptogenesis (26,58,59). Additional regulation of GABAergic neurons by SDF1␣ might function in the fine-tuning of synaptic circuitry.…”

CXCR4 signaling in the regulation of stem cell migration and development

“…The close juxtaposition of SDF-1 and CXCR4 in the adult DG suggests that CXCR4 may be an important regulator of adult neurogenesis in this part of the brain. Recent studies have demonstrated that SDF-1 is actually stored in neurotransmitter vesicles in DG neurons, including DG GABAergic interneurons such as Basket cells and granule cells (Tham et al, 2001). Both GABA and SDF-1 can be released in the DG and can regulate the functions of neural stem cells such as their proliferation (Bhattacharrya et al, unpublished observations).…”

Molecular Interaction between Projection Neuron Precursors and Invading Interneurons via Stromal-Derived Factor 1 (CXCL12)/CXCR4 Signaling in the Cortical Subventricular Zone/Intermediate Zone

“…Furthermore, it has been reported that stromal-derived factor 1 (SDF-1) is a chemoattractant for cortical interneurons that is expressed not in the cortex itself but exclusively by meningeal cells (Stumm et al, 2003). However, several groups have reported SDF-1-expressing cells in the deeper aspect of the embryonic neocortex (Tham et al, 2001;Tissir et al, 2004), and this expression was associated with invading prospective interneurons (Daniel et al, 2005).…”

“…During corticogenesis, SDF-1 has been shown to be specifically expressed in the meninges above the MZ as well as in a deep domain (Tham et al, 2001;Tissir et al, 2004;Daniel et al, 2005). Stumm et al (2003) examined the effects of SDF-1 or CXCR4 knock-out on interneuron migration at a late stage of embryonic development (E18.5) and attributed the observed misrouting of CXCR4-or Reelin-expressing interneurons exclusively to the lack of chemoattraction by meningeal SDF-1.…”