Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting.
Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting.
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DOI：
10.1186/s13064-021-00157-x
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发表时间：
2022-01-03
影响因子：
3.6
通讯作者：
Raper JA
中科院分区：
文献类型：
--
作者：
Cheng RP;Dang P;Taku AA;Moon YJ;Pham V;Sun X;Zhao E;Raper JA
嗅感觉神经元（OSN）轴突在发育的早期阶段从斑马鱼嗅上皮投射到嗅球中称为原肾小球的可重复的中间靶位置。表达OMP或TRPC 2的两类OSN专门靶向不同的互补原肾小球。使用RNAseq，我们确定了轴突导向受体nrp 2a和nrp 2b及其配体sema 3fa，作为这两类OSN之间差异表达的潜在导向因子。为了研究它们在OSN轴突导向中的作用，我们评估了在nrp 2a、nrp 2b或sema 3fa突变体中由OMP：RFP和TRPC 2：Venus转基因标记的OSN的肾小球靶向保真度。我们使用双突变和遗传相互作用实验来探究这三个基因之间的关系。我们使用实时延时成像来比较OSN生长锥在杂合子和突变体幼虫的肾小球靶向过程中的动态行为。在nrp 2a、nrp 2b或sema 3fa突变体中，TRPC 2类OSN的原肾小球靶向的保真度降低，因为轴突错误投射到OMP特异性原肾小球和球中的其他异位位置。这些错误预测进一步增强nrp 2a，nrp 2b双突变体表明，nrp 2的工作至少部分在同一指导过程中平行。遗传互作实验的结果与sema 3fa与nrp 2a和nrp 2b在相同的生物学途径中起作用是一致的。实时延时成像被用来检查TRPC 2类生长锥的动态行为相比，杂合子同胞nrp 2a突变体。一些TRPC 2类生长锥异位进入两组的球的背内侧区域，但在完全突变的胚胎，他们不太可能通过回缩纠正错误。当在sema 3fa杂合子和sema 3fa突变体幼虫之间比较TRPC 2类生长锥行为时，观察到相同的结果。我们的研究结果表明，nrp 2a和nrp 2b在TRPC 2类OSN中表达，有助于防止它们与OMP特异性原肾小球中的轴突投射混合，此外，sema 3fa有助于通过从背内侧球的排斥来排除TRPC 2类轴突。在线版本包含补充材料，可通过10.1186/s13064-021-00157-x获得。
Olfactory Sensory Neuron (OSN) axons project from the zebrafish olfactory epithelium to reproducible intermediate target locations in the olfactory bulb called protoglomeruli at early stages in development. Two classes of OSNs expressing either OMP or TRPC2 exclusively target distinct, complementary protoglomeruli. Using RNAseq, we identified axon guidance receptors nrp2a and nrp2b, and their ligand sema3fa, as potential guidance factors that are differentially expressed between these two classes of OSNs. To investigate their role in OSN axon guidance, we assessed the protoglomerular targeting fidelity of OSNs labeled by OMP:RFP and TRPC2:Venus transgenes in nrp2a, nrp2b, or sema3fa mutants. We used double mutant and genetic interaction experiments to interrogate the relationship between the three genes. We used live time-lapse imaging to compare the dynamic behaviors of OSN growth cones during protoglomerular targeting in heterozygous and mutant larvae. The fidelity of protoglomerular targeting of TRPC2-class OSNs is degraded in nrp2a, nrp2b, or sema3fa mutants, as axons misproject into OMP-specific protoglomeruli and other ectopic locations in the bulb. These misprojections are further enhanced in nrp2a;nrp2b double mutants suggesting that nrp2s work at least partially in parallel in the same guidance process. Results from genetic interaction experiments are consistent with sema3fa acting in the same biological pathway as both nrp2a and nrp2b. Live time-lapse imaging was used to examine the dynamic behavior of TRPC2-class growth cones in nrp2a mutants compared to heterozygous siblings. Some TRPC2-class growth cones ectopically enter the dorsal-medial region of the bulb in both groups, but in fully mutant embryos, they are less likely to correct the error through retraction. The same result was observed when TRPC2-class growth cone behavior was compared between sema3fa heterozygous and sema3fa mutant larvae. Our results suggest that nrp2a and nrp2b expressed in TRPC2-class OSNs help prevent their mixing with axon projections in OMP-specific protoglomeruli, and further, that sema3fa helps to exclude TRPC2-class axons by repulsion from the dorsal-medial bulb. The online version contains supplementary material available at 10.1186/s13064-021-00157-x.
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影响因子：
4.5
作者：
Dang P;Fisher SA;Stefanik DJ;Kim J;Raper JA
通讯作者：
Raper JA
影响因子：
16.2
作者：
Friedrich, RW;Korsching, SI
通讯作者：
Korsching, SI
影响因子：
16.2
作者：
Cloutier, JF;Giger, RJ;Ginty, DD
通讯作者：
Ginty, DD
影响因子：
5.8
作者：
Fernandez, Romain;Moisy, Cedric
通讯作者：
Moisy, Cedric
影响因子：
64.5
作者：
Komiyama, Takaki;Sweeney, Lora B.;Luo, Liqun
通讯作者：
Luo, Liqun