The Gata3 transcription factor is required for the survival of embryonic and adult sympathetic neurons.
The transcription factor Gata3 is essential for the development of sympathetic neurons and adrenal chromaffin cells. As Gata3 expression is maintained up to the adult stage, we addressed its function in differentiated sympathoadrenal cells at embryonic and adult stages by conditional Gata3 elimination. Inactivation of Gata3 in embryonic DBH-expressing neurons elicits a strong reduction in neuron numbers due to apoptotic cell death and reduced proliferation. No selective effect on noradrenergic gene expression (TH and DBH) was observed. Interestingly, Gata3 elimination in DBH-expressing neurons of adult animals also results in a virtually complete loss of sympathetic neurons. In the Gata3-deficient population, the expression of anti-apoptotic genes (Bcl-2, Bcl-xL, and NFkappaB) is diminished, whereas the expression of pro-apoptotic genes (Bik, Bok, and Bmf) was increased. The expression of noradrenergic genes (TH and DBH) is not affected. These results demonstrate that Gata3 is continuously required for maintaining survival but not differentiation in the sympathetic neuron lineage up to mature neurons of adult animals.
Tsarovina
Konstantina
K
Research Group Developmental Neurobiology, Max-Planck-Institute for Brain Research, 60528 Frankfurt/M, Germany.
Reiff
Tobias
T
Stubbusch
Jutta
J
Kurek
Dorota
D
Grosveld
Frank G
FG
Parlato
Rosanna
R
Schütz
Günther
G
Rohrer
Hermann
H
D000367:Age Factors; D000818:Animals; D002135:Calcium-Binding Proteins; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D019439:Chromaffin Cells / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D050777:Stathmin; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002135:Calcium-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C109220:NBPhox protein; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D050777:Stathmin; C512849:Stmn2 protein, mouse; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D020917:Receptor, trkA; D053148:Caspase 3; D004296:Dopa Decarboxylase