Regulation of the LIM-type homeobox gene islet-1 during neuronal regeneration

• Published in: Neuroscience 1999-02, Vol.88 (3), p.917-925
• Main Authors: Hol, E.M, Schwaiger, F.-W, Werner, A, Schmitt, A, Raivich, G, Kreutzberg, G.W
• Format: Article
• Language: English
• Subjects: Animals; Axotomy; Biological and medical sciences; Development. Senescence. Regeneration. Transplantation; Facial Nerve - physiology; Fundamental and applied biological sciences. Psychology; GAP-43 Protein - genetics; Gene Expression Regulation; Genes, Homeobox; Homeodomain Proteins - genetics; LIM-Homeodomain Proteins; LIM-type homeobox genes; Male; Microscopy, Confocal; motoneurons; Motor Neurons - metabolism; Nerve Regeneration - physiology; Nerve Tissue Proteins - genetics; Neurons - metabolism; Neurons, Afferent - metabolism; Peptidylprolyl Isomerase - genetics; peripheral nerve lesion; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Sciatic Nerve - metabolism; sensory neurons; Time Factors; transcription factor; Transcription Factors; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00263-2

Peripheral nerve lesion leads to prominent changes in gene expression in the injured neurons, a process co-ordinated by transcription factors. During development the transcription factor islet-1 plays an important role in differentiation and axogenesis. In axotomized adult neurons a process of axonal regrowth and re-establishment of the neuronal function has to be activated. Thus, we studied changes in the expression of islet-1 after axotomy, under the assumption that frequently developmentally-regulated factors are re-activated during neuronal regeneration. We investigated the regulation of islet-1 expression with (i) semi-quantitative reverse transcription polymerase chain reaction and (ii) confocal microscopy in combination with quantitative image analysis. Islet-1 expression was suprisingly down-regulated in motoneurons and sensory neurons of adult rats after axotomy. A maximal reduction in the expression level was reached between day 3 and 7 after nerve lesion, a period of extensive axonal sprouting. Islet-1 expression attained control level at day 42 after lesion, a time-point at which target re-innervation takes place. The decreased expression of islet-1 during axonal regeneration is in contrast to the high levels of islet-1 expression during axogenesis in the developing nervous system. Thus, the proposed role of islet-1 in axonal target finding during axogenesis could not be confirmed in the adult rat. The observed down-regulation of islet-1 rather suggests, that the activation of downstream genes important for the embryonic pattern of axonal path finding is suppressed. Moreover, in the adult nervous system islet-1 might be one of the transcription factors regulating the expression of proteins significant for the physiological intact neuronal phenotype.