Regulation of the LIM-type homeobox gene islet-1 during neuronal regeneration.
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 reactivated 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 reinnervation 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.
Hol
E M
EM
Department of Neuromorphology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Schwaiger
F W
FW
Werner
A
A
Schmitt
A
A
Raivich
G
G
Kreutzberg
G W
GW
D000818:Animals; D019771:Axotomy; D005154:Facial Nerve / Q000502:physiology*; D019922:GAP-43 Protein / Q000235:genetics; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D008297:Male; D018613:Microscopy, Confocal; D009046:Motor Neurons / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors
D019922:GAP-43 Protein; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D019696:Peptidylprolyl Isomerase