Misregulation of SDF1-CXCR4 signaling impairs early cardiac neural crest cell migration leading to conotruncal defects.

RATIONALE: Cardiac neural crest cells (NCs) contribute to heart morphogenesis by giving rise to a variety of cell types from mesenchyme of the outflow tract, ventricular septum, and semilunar valves to neurons of the cardiac ganglia and smooth muscles of the great arteries. Failure in cardiac NC development results in outflow and ventricular septation defects commonly observed in congenital heart diseases. Cardiac NCs derive from the vagal neural tube, which also gives rise to enteric NCs that colonize the gut; however, so far, molecular mechanisms segregating these 2 populations and driving cardiac NC migration toward the heart have remained elusive. OBJECTIVE: Stromal-derived factor-1 (SDF1) is a chemokine that mediates oriented migration of multiple embryonic cells and mice deficient for Sdf1 or its receptors, Cxcr4 and Cxcr7, exhibit ventricular septum defects, raising the possibility that SDF1 might selectively drive cardiac NC migration toward the heart via a chemotactic mechanism. METHODS AND RESULTS: We show in the chick embryo that Sdf1 expression is tightly coordinated with the progression of cardiac NCs expressing Cxcr4. Cxcr4 loss-of-function causes delayed migration and enhanced death of cardiac NCs, whereas Sdf1 misexpression results in their diversion from their normal pathway, indicating that SDF1 acts as a chemoattractant for cardiac NCs. These alterations of SDF1 signaling result in severe cardiovascular defects. CONCLUSIONS: These data identify Sdf1 and its receptor Cxcr4 as candidate genes responsible for cardiac congenital pathologies in human.

Intrinsic properties guide proximal abducens and oculomotor nerve outgrowth in avian embryos.

Proper movement of the vertebrate eye requires the formation of precisely patterned axonal connections linking cranial somatic motoneurons, located at defined positions in the ventral midbrain and hindbrain, with extraocular muscles. The aim of this research was to assess the relative contributions of intrinsic, population-specific properties and extrinsic, outgrowth site-specific cues during the early stages of abducens and oculomotor nerve development in avian embryos. This was accomplished by surgically transposing midbrain and caudal hindbrain segments, which had been pre-labeled by electroporation with an EGFP construct. Graft-derived EGFP+ oculomotor axons entering a hindbrain microenvironment often mimicked an abducens initial pathway and coursed cranially. Similarly, some EGFP+ abducens axons entering a midbrain microenvironment mimicked an oculomotor initial pathway and coursed ventrally. Many but not all of these axons subsequently projected to extraocular muscles that they would not normally innervate. Strikingly, EGFP+ axons also took initial paths atypical for their new location. Upon exiting from a hindbrain position, most EGFP+ oculomotor axons actually coursed ventrally and joined host branchiomotor nerves, whose neurons share molecular features with oculomotor neurons. Similarly, upon exiting from a midbrain position, some EGFP+ abducens axons turned caudally, elongated parallel to the brainstem, and contacted the lateral rectus muscle, their originally correct target. These data reveal an interplay between intrinsic properties that are unique to oculomotor and abducens populations and shared ability to recognize and respond to extrinsic directional cues. The former play a prominent role in initial pathway choices, whereas the latter appear more instructive during subsequent directional choices.

Oligodendrocyte precursors originate in the parabasal band of the basal plate in prosomere 1 and migrate into the alar prosencephalon during chick development.

Oligodendrocytes are the myelin-forming cells in the central nervous system of vertebrates. Oligodendrocyte precursors arise from multiple restricted foci distributed along the antero-posterior axis of the developing brain. In chick and mouse embryos, oligodendrocyte precursors of the anterior forebrain emerge from neuroepithelial cells of the subpallium and migrate tangentially to invade the entire telencephalon (Olivier et al. (2001) Development 128:1757-1769). In the diencephalon, oligodendrocyte neuroepithelial precursors seem to be mainly located in the basal plate of caudal prosomeres, but very little is known about their distribution and maturation at later stages of embryonic development. Thus, in this work, we studied the origin and migration of oligodendrocyte precursos in the diencephalon of quail-chick chimeras. Homotopic and homochronic grafts demonstrated that, during embryonic development, diencephalic oligodendrocytes emerge from a common neuroepithelial domain in the basal plate of prosomere 1 and migrate tangentially, invading the dorsal regions of the diencephalic prosomeres and the telencephalon.