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Departments of
*
Pharmacology and Toxicology and
Biochemistry, University of Ulm, Ulm, Germany
Transmembrane signaling of the CXC chemokine stromal cell-derived
factor-1 (SDF-1) is mediated by CXCR4, a G protein-coupled receptor
initially identified in leukocytes and shown to serve as a coreceptor
for the entry of HIV into lymphocytes. Characterization of SDF-1- and
CXCR4-deficient mice has revealed that SDF-1 and CXCR4 are of vital
developmental importance. To study the role of the
SDF-1/CXCR4-chemokine/receptor system as a regulator of vertebrate
development, we isolated and characterized a cDNA encoding SDF-1 of the
lower vertebrate Xenopus laevis (xSDF-1). Recombinant
xSDF-1 was produced in insect cells, purified, and functionally
characterized. Although xSDF-1 is only 64–66% identical with its
mammalian counterparts, it is indistinguishable from human (h)SDF-1
in terms of activating both X. laevis CXCR4 and hCXCR4.
Thus, both xSDF-1 and hSDF-1 promoted CXCR4-mediated activation of
heterotrimeric Gi2 in a cell-free system and induced
release of intracellular calcium ions in and chemotaxis of intact
lymphoblastic cells. Analysis of the time course of xSDF-1 mRNA
expression during Xenopus embryogenesis revealed a
tightly coordinated regulation of xSDF-1 and X. laevis
CXCR4. xSDF-1 mRNA was specifically detected in the developing CNS,
incipient sensory organs, and the embryonic heart. In
Xenopus, CXCR4 mRNA appears to be absent from the heart
anlage, but present in neural crest cells. This observation suggests
that xSDF-1 expressed in the heart anlage may attract cardiac neural
crest cells expressing CXCR4 to migrate to the primordial heart to
regulate both septation of the cardiac outflow tract and
differentiation of the myocardium during early heart
development.
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  R. Stumm and V. Hollt CXC chemokine receptor 4 regulates neuronal migration and axonal pathfinding in the developing nervous system: implications for neuronal regeneration in the adult brain J. Mol. Endocrinol., March 1, 2007; 38(3): 377 - 382. [Abstract] [Full Text] [PDF]
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 M. Suzuki, Y. Takamura, M. Maeno, S. Tochinai, D. Iyaguchi, I. Tanaka, J. Nishihira, and T. Ishibashi Xenopus laevis Macrophage Migration Inhibitory Factor Is Essential for Axis Formation and Neural Development J. Biol. Chem., May 14, 2004; 279(20): 21406 - 21414. [Abstract] [Full Text] [PDF]
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