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Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve.

ABSTRACT: Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ligands for the transmembrane receptor neuropilin 1 (Nrp1), the semaphorin Sema3A and the VEGF164 isoform of Vascular Endothelial Growth Factor. Although Sema3A is known to control the guidance of facial nerve axons, we now show that it is not required for the pathfinding of their somata. Vice versa, we find that VEGF164 is not required for axon guidance of facial motor neurons, but is essential for the correct migration of their somata. These observations demonstrate, for the first time, that VEGF contributes to neuronal patterning in vivo, and that different compartments of one cell can be co-ordinately patterned by structurally distinct ligands for a shared receptor.

SUBMITTER: Schwarz Q

PROVIDER: S-EPMC528901 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature

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Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve.

Schwarz Quenten Q Gu Chenghua C Fujisawa Hajime H Sabelko Kimberly K Gertsenstein Marina M Nagy Andras A Taniguchi Masahiko M Kolodkin Alex L AL Ginty David D DD Shima David T DT Ruhrberg Christiana C

Genes & development 20041101 22

Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ligands for the transmembrane receptor neuropilin 1 (Nrp1), the semaphorin Sema3A and the VEGF164 isoform of Vascular Endothelial Growth Facto ...[more]

PMID: 15545635

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Project description:Facial vascular anomalies are surgical challenges due to their vascularity and facial nerve distortion. To assist facial vascular anomaly surgical treatment, presurgical percutaneous facial nerve stimulation and recording of compound motor action potentials can be used to map the facial nerve branches. During surgery, the nerve map and continuous intraoperative motor end plate potential monitoring can be used to reduce nerve injury.To investigate if preoperative facial nerve mapping (FNM) is associated with intraoperative facial nerve injury risk and safe surgical approach options compared with standard nerve integrity monitoring (NIM).This investigation was a historically controlled study at a tertiary vascular anomaly center in Seattle, Washington. Participants were 92 pediatric patients with facial vascular anomalies undergoing definitive anomaly surgery (from January 1, 1999, through January 1, 2015), with 2 years' follow-up. In retrospective review, a consecutive FNM patient cohort after 2005 (FNM group) was compared with a consecutive historical cohort (1999-2005) (NIM group).Postoperative facial nerve function and selected surgical approach. For NIM and FNM comparisons, statistical analysis calculated odds ratios of nerve injury and operative approach, and time-to-event methods analyzed operative time.The NIM group had 31 patients (median age, 3.3 years [interquartile range, 2.2-11.4 years]; 20 [65%] male), and the FNM group had 61 patients (median age, 4.4 years [interquartile range, 1.5-11.0 years]; 26 [43%] male). In both groups, lymphatic malformation resection was most common (19 of 31 [61%] in the NIM group and 32 of 61 [52%] in the FNM group), and the median anomaly volumes were similar (52.4 mL; interquartile range, 12.8-183.3 mL in the NIM group and 65.4 mL; interquartile range, 18.8-180.2 mL in the FNM group). Weakness in the facial nerve branches at 2 years after surgery was more common in the NIM group (6 of 31 [19%]) compared with the FNM group (1 of 61 [2%]) (percentage difference, 17%; 95% CI, 3%-32%). Anterograde facial nerve dissection was used more in the NIM group (27 of 31 [87%]) compared with the FNM group (28 of 61 [46%]) (percentage difference, 41%; 95% CI, 24%-58%). Treatment with retrograde dissection without identification of the main trunk of the facial nerve was performed in 21 of 61 (34%) in the FNM group compared with 0 of 31 (0%) in the NIM group. Operative time was significantly shorter in the FNM group, and patients in the FNM group were more likely to complete surgery sooner (adjusted hazard ratio, 5.36; 95% CI, 2.00-14.36).Facial nerve mapping before facial vascular anomaly surgery was associated with less intraoperative facial nerve injury and shorter operative time. Mapping enabled direct identification of individual intralesional and perilesional nerve branches, reducing the need for traditional anterograde facial nerve dissection, and allowed for safe removal of some lesions after partial nerve dissection through transoral or direct excision.

Dataset Information

Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve.

Publications

Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve.

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