Cranial sensory ganglia neurons require intrinsic N-cadherin function for guidance of afferent fibers to their final targets.
Cell adhesion molecules, such as N-cadherin (cdh2), are essential for normal neuronal development, and as such have been implicated in an array of processes including neuronal differentiation and migration, and axon growth and fasciculation. cdh2 is expressed in neurons of the peripheral nervous system during development, but its role in these cells during this time is poorly understood. Using the transgenic zebrafish line, tg(p2xr3.2:eGFP(sl1)), we have examined the involvement of cdh2 in the formation of sensory circuits by the peripheral nervous system. The tg(p2xr3.2:eGFP(sl1)) fish allows visualization of neurons comprising the trigeminal, facial, glossopharyngeal and vagal ganglia and their axons throughout development. Reduction of cdh2 in this line was achieved by either crosses to the cdh2-mutant strain, glass onion (glo) or injection of a cdh2 morpholino (MO) into single-cell embryos. Here we show that cdh2 function is required to alter the directional vectors of growing axons upon reaching intermediate targets. The central axons enter the hindbrain appropriately but fail to turn caudally towards their final targets. Similarly, the peripheral axons extend ventrally, but fail to turn and project along a rostral/caudal axis. Furthermore, by expressing dominant negative cdh2 constructs selectively within cranial sensory ganglia (CSG) neurons, we found that cdh2 function is necessary within the axons to elicit these stereotypic turns, thus demonstrating that cdh2 acts cell autonomously. Together, our in vivo data reveal a novel role for cdh2 in the establishment of circuits by peripheral sensory neurons.
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
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D000344:Afferent Pathways / Q000196:embryology / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000196:embryology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D004525:Efferent Pathways / Q000196:embryology; D017950:Ganglia, Sensory / Q000166:cytology / Q000196:embryology*; D055785:Gene Knockdown Techniques; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009475:Neurons, Afferent / Q000502:physiology*; D009476:Neurons, Efferent / Q000502:physiology; D010641:Phenotype; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; C513786:N-cadherin, zebrafish; D029961:Zebrafish Proteins