PMID- 16887884 OWN - NLM STAT- MEDLINE DCOM- 20070212 LR - 20061026 IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 20 IP - 11 DP - 2006 Nov TI - In vivo induction of glial cell proliferation and axonal outgrowth and myelination by brain-derived neurotrophic factor. PG - 2987-98 AB - Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of neuronal cell survival and differentiation factors but is thought to be involved in neuronal cell proliferation and myelination as well. To explore the role of BDNF in vivo, we employed the intermediate pituitary melanotrope cells of the amphibian Xenopus laevis as a model system. These cells mediate background adaptation of the animal by producing high levels of the prohormone proopiomelanocortin (POMC) when the animal is black adapted. We used stable X. transgenesis in combination with the POMC gene promoter to generate transgenic frogs overexpressing BDNF specifically and physiologically inducible in the melanotrope cells. Intriguingly, an approximately 25-fold overexpression of BDNF resulted in hyperplastic glial cells and myelinated axons infiltrating the pituitary, whereby the transgenic melanotrope cells became located dispersed among the induced tissue. The infiltrating glial cells and axons originated from both peripheral and central nervous system sources. The formation of the phenotype started around tadpole stage 50 and was induced by placing white-adapted transgenics on a black background, i.e. after activation of transgene expression. The severity of the phenotype depended on the level of transgene expression, because the intermediate pituitaries from transgenic animals raised on a white background or from transgenics with only an approximately 5-fold BDNF overexpression were essentially not affected. In conclusion, we show in a physiological context that, besides its classical role as neuronal cell survival and differentiation factor, in vivo BDNF can also induce glial cell proliferation as well as axonal outgrowth and myelination. FAU - de Groot, Dorien M AU - de Groot DM AD - Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands. FAU - Coenen, Anton J M AU - Coenen AJ FAU - Verhofstad, Albert AU - Verhofstad A FAU - van Herp, Francois AU - van Herp F FAU - Martens, Gerard J M AU - Martens GJ LA - eng PT - Comparative Study PT - Journal Article DEP - 20060803 PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Axons/*physiology MH - Brain-Derived Neurotrophic Factor/genetics/metabolism/*physiology MH - *Cell Proliferation MH - Embryo, Nonmammalian MH - Embryonic Induction MH - Gene Expression Regulation, Developmental MH - Melanotrophs/metabolism MH - Models, Biological MH - Myelin Sheath/*metabolism MH - Nerve Fibers, Myelinated/physiology MH - Nerve Growth Factors/physiology MH - Neurites/*physiology MH - Neuroglia/*physiology MH - Organ Specificity MH - Pituitary Gland/anatomy & histology/embryology MH - Pituitary Gland, Intermediate/embryology/metabolism MH - Transgenes/physiology MH - Xenopus laevis/embryology/physiology EDAT- 2006/08/05 09:00 MHDA- 2007/02/13 09:00 CRDT- 2006/08/05 09:00 PHST- 2006/08/05 09:00 [pubmed] PHST- 2007/02/13 09:00 [medline] PHST- 2006/08/05 09:00 [entrez] AID - me.2006-0168 [pii] AID - 10.1210/me.2006-0168 [doi] PST - ppublish SO - Mol Endocrinol. 2006 Nov;20(11):2987-98. doi: 10.1210/me.2006-0168. Epub 2006 Aug 3.