title: Essential requirement for zebrafish anosmin-1a in the migration of the posterior lateral line primordium.
abstract: Kallmann syndrome (KS) is a human genetic disease that impairs both cell migration and axon elongation. The KAL-1 gene underlying the X-linked form of KS, encodes an extracellular matrix protein, anosmin-1, which mediates cell adhesion and axon growth and guidance in vitro. We investigated the requirement for kal1a and kal1b, the two orthologues of the KAL-1 gene in zebrafish, in the journey of the posterior lateral line primordium (PLLP). First, we established that while the accumulation of kal1a and kal1b transcripts was restricted to the posterior region of the migrating primordium and newly deposited neuromasts, the encoded proteins, anosmin-1a and anosmin-1b, respectively, were accumulated in the PLLP, in differentiated neuromasts and in a thin strip extending along the trail path of the PLLP. We also show that morpholino knockdown of kal1a, but not kal1b, severely impairs PLLP migration. However, while the PLLP of kal1a morphants displays highly abnormal morphology, proper expression of the cxcr4b gene suggests that kal1a does not play a role in PLLP differentiation. Conversely, wild-type levels of kal1a transcripts are detected in the PLLP of cxcr4b or sdf1a morphant embryos, strongly suggesting that kal1a transcription is independent of CXCR4b/SDF1a signalling. Last, moderate depletion of both anosmin-1a and SDF1a markedly affects PLLP migration providing strong evidence that anosmin-1a acts as an essential co-factor in SDF1a-mediated signalling pathways. Our findings, which demonstrate, for the first time, an essential requirement for anosmin-1a in PLLP migration, also strongly suggest that this protein plays a key role for proper activation of the CXCR4b/SDF1a and/or CXCR7/SDF1a signalling pathway in PLLP migration.
authors.affiliation: INSERM Equipe Avenir, IFR Neurosciences (IFR 70), Hôpital de la Pitié-Salpêtrière, 47 Bd de l'Hôpital, Paris, F-75651, France.
authors.forename: Constantin
authors.initials: C
authors.lastname: Yanicostas
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ernest
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Dayraud
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Nadia
authors.initials: N
authors.lastname: Soussi-Yanicostas
mesh_terms: D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D016326:Extracellular Matrix Proteins / Q000145:classification / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D054387:Receptors, CXCR / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: C519524:CXCR7 protein, zebrafish; D054377:Chemokine CXCL12; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D029961:Zebrafish Proteins; C531179:anos1a protein, zebrafish