Cxcl12/Cxcr4 chemokine signaling is required for placode assembly and sensory axon pathfinding in the zebrafish olfactory system

Abstract

Positioning neurons in the right places and wiring axons to the appropriate targets are essential events for establishment of neural circuits. In the zebrafish olfactory system, precursors of olfactory sensory neurons (OSNs) assemble into a compact cluster to form the olfactory placode. Subsequently, OSNs differentiate and extend their axons to the presumptive olfactory bulb with high precision. In this study, we aim to elucidate the molecular mechanism underlying these two developmental processes. cxcr4b, encoding a chemokine receptor, is expressed in the migrating olfactory placodal precursors, and cxcl12a (SDF-1a), encoding a ligand for Cxcr4b, is expressed in the abutting anterior neural plate. The expression of cxcr4b persists in the olfactory placode at the initial phase of OSN axon pathfinding. At this time, cxcl12a is expressed along the placode-telencephalon border and at the anterior tip of the telencephalon, prefiguring the route and target of OSN axons, respectively. Interfering with Cxcl12a/Cxcr4b signaling perturbs the assembly of the olfactory placode, resulting in the appearance of ventrally displaced olfactory neurons. Moreover, OSN axons frequently fail to exit the olfactory placode and accumulate near the placode-telencephalon border in the absence of Cxcr4b-mediated signaling. These data indicate that chemokine signaling contributes to both the olfactory placode assembly and the OSN axon pathfinding in zebrafish.

Comparison of carnivore, omnivore, and herbivore mammalian genomes with a new leopard assembly

“…CXCL12 (stromal cell-derived factor 1), which was found as a shared PSG in carnivores, is known to influence the guidance of both migrating neurons and growing axons. CXCL12 / CXCR4 signaling has been shown to regulate motor axon projection in the mouse [41, 42]. Two other carnivore-shared PSGs, DMP1 and PTN , are known to play an important role in bone development and repair [43, 44].…”

Attractive guidance: How the chemokine SDF1/CXCL12 guides different cells to different locations

“…In the immune system, CXCR4-mediated SDF1 signaling attracts lymphocytes [13], stimulates the proliferation of blood cells [17][18][19] and contributes to the homing of hematopoietic stem cells [20]. These guidance functions are also critical in the developing embryo where SDF1 guides Cxcr4 -expressing germ cells [21][22][23], cells of the posterior lateral line primordium [24] and blood vessels [25][26], dentate gyrus granule cells [27][28], trigeminal [29] and dorsal root ganglia sensory neurons [30], gonadotropin-releasing hormone neurons [31] and olfactory neurons [32]. SDF1 also controls the spreading of interneurons [33][34][35][36] and Cajal-Retzius cells across the cortex [37][38], retains cerebellar external granule cells at their intermediate target [39][40][18][19][41] and anchors endoderm cells to the adjacent mesoderm during gastrulation [42][43].…”

Integrin-α5 Coordinates Assembly of Posterior Cranial Placodes in Zebrafish and Enhances Fgf-Dependent Regulation of Otic/Epibranchial Cells

“…For example, precursors of the anterior pituitary, olfactory and lens placodes are initially intermixed but subsequently sort out to form their respective placodes [9]–[12]. In the case of the olfactory placode, precursors converge into a compact placode via chemotaxis mediated by the Sdf1-Cxcr4 chemokine signaling pathway [13]. Similarly, trigeminal precursors are initially widely scattered but then undergo Sdf1/Cxcr4-dependent chemotaxis to converge into a coherent placode [14].…”