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神经营养因子受体基因在发育中的背根神经节中以不同模式表达。

Neurotrophin receptor genes are expressed in distinct patterns in developing dorsal root ganglia.

作者信息

Mu X, Silos-Santiago I, Carroll S L, Snider W D

机构信息

Department of Neurology, Washington University Medical School, St. Louis, Missouri 63110.

出版信息

J Neurosci. 1993 Sep;13(9):4029-41. doi: 10.1523/JNEUROSCI.13-09-04029.1993.

Abstract

All members of the neurotrophin family of neuronal growth factors promote survival and neurite outgrowth of dorsal root ganglion (DRG) neurons in vitro. The trk family of protooncogenes encodes receptors that are now thought to mediate the biological effects of neurotrophins. In order to learn more about the dependence of DRG neurons on neurotrophins in vivo, we have studied mRNA expression of members of the trk family in developing DRGs in embryonic and postnatal rats. We show here that neurotrophin receptors are expressed in thoracic and lumbar DRGs by embryonic day 13 (E13), which is only 24-48 hr after neurogenesis begins in these ganglia. Distinct patterns of expression of trkA, trkB, and trkC are readily apparent by E15. At this age, 40% of thoracic DRG neurons express trkA. In contrast, trkB and trkC are expressed by only 6% and 8%, respectively, of thoracic DRG neurons. These percentages change little between E15 and postnatal day 1. Although absolute numbers of DRG neurons expressing neurotrophin receptors are greater in lumbar than in thoracic ganglia, the ratios of DRG neurons expressing different members of the trk family are similar in the two regions. The different trks are expressed by distinct populations of DRG neurons from E15 onward. trkA is expressed predominantly by small neurons with darkly staining cytoplasm. trkB and trkC are expressed by large, lightly staining neurons. Size-frequency histograms show that trkA is expressed by neurons of variable sizes, but particularly by neurons at the smallest end of the spectrum. In contrast, trkC is expressed predominantly by large DRG neurons, including those with the largest soma areas. trkB is expressed by DRG neurons of intermediate size. Our results show that a majority of DRG neurons express mRNA for at least one member of the trk protooncogene family. Furthermore, trk expression occurs in a time frame consistent with the idea that trks mediate responses of DRG neurons to neurotrophins that are synthesized in both the periphery and spinal cord at early developmental stages. Finally, different populations of DRG neurons express different trks. We hypothesize that DRG neurons subserving different functions express different trks, and that trk expression of a particular class of DRG neurons determines its neurotrophin dependence during development.

摘要

神经营养因子家族的所有成员均可在体外促进背根神经节(DRG)神经元的存活和轴突生长。原癌基因trk家族编码的受体目前被认为介导神经营养因子的生物学效应。为了更深入了解DRG神经元在体内对神经营养因子的依赖性,我们研究了胚胎期和出生后大鼠发育中的DRG中trk家族成员的mRNA表达。我们在此表明,在胚胎第13天(E13)时,胸段和腰段DRG中就表达神经营养因子受体,而此时这些神经节的神经发生才开始24 - 48小时。到E15时,trkA、trkB和trkC的不同表达模式已清晰可见。在这个年龄段,40%的胸段DRG神经元表达trkA。相比之下,胸段DRG神经元中分别只有6%和8%表达trkB和trkC。从E15到出生后第1天,这些百分比变化不大。虽然表达神经营养因子受体的DRG神经元的绝对数量在腰段神经节中比胸段神经节中多,但在这两个区域中表达trk家族不同成员的DRG神经元的比例相似。从E15开始,不同的trk由不同群体的DRG神经元表达。trkA主要由细胞质染色深的小神经元表达。trkB和trkC由大的、染色浅的神经元表达。大小频率直方图显示,trkA由大小不一的神经元表达,但特别是频谱中最小端的神经元。相比之下,trkC主要由大的DRG神经元表达,包括那些胞体面积最大的神经元。trkB由中等大小的DRG神经元表达。我们的结果表明,大多数DRG神经元表达trk原癌基因家族至少一个成员的mRNA。此外,trk的表达发生在一个与trk介导DRG神经元对早期发育阶段在外周和脊髓中合成的神经营养因子的反应这一观点相一致的时间框架内。最后,不同群体的DRG神经元表达不同的trk。我们假设,发挥不同功能的DRG神经元表达不同的trk,并且特定类别的DRG神经元的trk表达决定了其在发育过程中的神经营养因子依赖性。

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