The facial motor nucleus transcriptional program in response to peripheral nerve injury identifies Hn1 as a regeneration-associated gene.
Facial nerve axotomy (FNA) is a well-established experimental model of motoneuron regeneration. After peripheral nerve axotomy, a sequence of events including glial activation and axonal regrowth leads to functional recovery of the afflicted pool of motoneurons. Using microarray analysis we identified an increase in the expression of 60 genes (at a false discovery rate of 0.1, genes were significant P < 0.004) within the facial nucleus as a consequence of nerve injury. In situ hybridization analysis validated the increased expression of many of these axotomy-induced genes. One specific gene, encoding a unique primary amino acid sequence, termed hemopoietic- and neurologic-expressed sequence-1 (Hn1), was evaluated more extensively using several additional nerve injury paradigms. Hn1 mRNA was upregulated in injured facial motoneurons in both rats and mice. Sustained upregulation of Hn1 mRNA was evident after nerve resection whereas levels of Hn1 mRNA returned to baseline in animals subjected to nerve crush or nerve transection. Hn1 was also increased in the dorsal motor nucleus and the nucleus ambiguous after vagus nerve axotomy, another regeneration model. No upregulation of Hn1 expression was observed, however, in two nonregeneration models: FNA in newborn rats and rubrospinal tractotomy. Hn1 mRNA was ubiquitous in the developing central nervous system whereas its expression in adult brain was confined to neurons of the hippocampus, cortex and cerebellum. These findings identify Hn1 as a gene associated with nervous system development and nerve regeneration.
Zujovic
Violetta
V
Department of Pharmacology and Therapeutics, University of Florida College of Medicine,Gainesville, Florida 32610-0267, USA.
Luo
Defang
D
Baker
Henry V
HV
Lopez
M Cecilia
MC
Miller
Kelly R
KR
Streit
Wolfgang J
WJ
Harrison
Jeffrey K
JK
D000818:Animals; D019771:Axotomy; D018797:Cell Cycle Proteins; D005154:Facial Nerve / Q000166:cytology / Q000378:metabolism*; D020220:Facial Nerve Injuries / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins; D009046:Motor Neurons / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000166:cytology / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism; D020421:Vagus Nerve Diseases / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; C108200:Jpt1 protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger