Anosmin-1a is required for fasciculation and terminal targeting of olfactory sensory neuron axons in the zebrafish olfactory system.
The KAL-1 gene underlies the X-linked form of Kallmann syndrome (KS), a neurological disorder that impairs the development of the olfactory and GnRH systems. KAL-1 encodes anosmin-1, a cell matrix protein that shows cell adhesion, neurite outgrowth, and axon-guidance and -branching activities. We used zebrafish embryos as model to better understand the role of this protein during olfactory system (OS) development. First, we detected the protein in olfactory sensory neurons from 22 h post-fertilization (hpf) onward, i.e. prior their pioneer axons reached presumptive olfactory bulbs (OBs). We found that anosmin-1a depletion impaired the fasciculation of olfactory axons and their terminal targeting within OBs. Last, we showed that kal1a inactivation induced a severe decrease in the number of GABAergic and dopaminergic OB neurons. Though the phenotypes induced following anosmin-1a depletion in zebrafish embryos did not match precisely the defects observed in KS patients, our results provide the first demonstration of a direct requirement for anosmin-1 in OS development in vertebrates and stress the role of OB innervation on OB neuron differentiation.
Yanicostas
Constantin
C
Centre de Recherche de l'Institut du Cerveau et de la Moëlle épinière, Paris, France.
Herbomel
Eric
E
Dipietromaria
Aurélie
A
Soussi-Yanicostas
Nadia
N
D000818:Animals; D030801:Animals, Genetically Modified / Q000196:embryology / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000294:innervation / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics; D009830:Olfactory Bulb / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D009831:Olfactory Mucosa / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D009833:Olfactory Pathways / Q000196:embryology / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000196:embryology* / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism; D021381:Protein Transport; D011984:Sensory Receptor Cells / Q000145:classification / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D029961:Zebrafish Proteins; C531179:anos1a protein, zebrafish