Isoform-specific role of transforming growth factor-beta2 in the regulation of proliferation and differentiation of murine adrenal chromaffin cells in vivo.
Chromaffin cells, the neuroendocrine cells of the adrenal medulla, play an important role in molecular, cellular, and developmental neurobiology. Unlike the closely related sympathetic neurons, chromaffin cells are able to proliferate throughout their whole life span. Proliferation of chromaffin cells in vivo is thought to be regulated by the interaction of neurogenic and hormonal signals. Previous studies have shown that chromaffin cells synthesize and release transforming growth factor-betas (TGF-betas). In the present study, effects of TGF-betas on proliferation and differentiation of chromaffin cells in mouse adrenal chromaffin cells were investigated in a genetic mouse model. We observed a significant increase in the total number of tyrosine hydroxylase-positive (TH(+)) cells in Tgfbeta2(-/-) knockout mouse embryos at embryonic day (E) 18.5 compared with wild-type animals (Tgfbeta2(+/+)), but no changes in the number of TH(+) cells were observed in Tgfbeta3(-/-) mouse mutants. At E15.5, but not at E18.5, there was a marked increase in the number of proliferative cell nuclear antigen-positive chromaffin cells in Tgfbeta2(-/-) knockout embryos compared with the wild-type group. On the other hand, there was a clear decrease in the ratio of total number of phenylethanolamine-N-methyltransferase-positive cells to the total TH(+) in Tgfbeta2(-/-) mice embryos at E18.5 compared with wild-type animals. This is the first documentation of the physiological significance of the TGF-beta2, an isoform that has been suggested to play a role in the regulation of chromaffin cells proliferation and differentiation based on in vitro experiments.
Department of Neuroanatomy, Medical Faculty, University Goettingen, D-37075 Goettingen, Germany.
Belal
B
Rahhal
Nicole
N
Dünker
Stephanie
S
Combs
Kerstin
K
Krieglstein
D000313:Adrenal Medulla / Q000166:cytology; D000367:Age Factors; D000818:Animals; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000502:physiology*; D004622:Embryo, Mammalian; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020033:Protein Isoforms / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000502:physiology*; D053781:Transforming Growth Factor beta2; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D014446:Tyrosine 3-Monooxygenase; D010625:Phenylethanolamine N-Methyltransferase