Zinc finger protein too few controls the development of monoaminergic neurons.
The mechanism controlling the development of dopaminergic (DA) and serotonergic (5HT) neurons in vertebrates is not well understood. Here we characterized a zebrafish mutant--too few (tof)--that develops hindbrain 5HT and noradrenergic neurons, but does not develop hypothalamic DA and 5HT neurons. tof encodes a forebrain-specific zinc finger transcription repressor that is homologous to the mammalian Fezl (forebrain embryonic zinc finger-like protein). Mosaic and co-staining analyses showed that fezl was not expressed in DA or 5HT neurons and instead controlled development of these neurons non-cell-autonomously. Both the eh1-related repressor motif and the second zinc finger domain were necessary for tof function. Our results indicate that tof/fezl is a key component in regulating the development of monoaminergic neurons in the vertebrate brain.
Levkowitz
Gil
G
Rinat Neuroscience Corporation, 3155 Porter Drive, Palo Alto, California 94304, USA. gillev@rinatneuro.com
Zeller
Jörg
J
Sirotkin
Howard I
HI
French
Dorothy
D
Schilbach
Sarah
S
Hashimoto
Hisashi
H
Hibi
Masahiko
M
Talbot
William S
WS
Rosenthal
Arnon
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D017209:Apoptosis / Q000235:genetics; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D016380:Brain Tissue Transplantation; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification*; D002454:Cell Differentiation / Q000235:genetics*; D002874:Chromosome Mapping; D004298:Dopamine / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D054848:Peptaibols; D010455:Peptides; D012097:Repressor Proteins / Q000235:genetics / Q000302:isolation & purification; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins; D016335:Zinc Fingers / Q000235:genetics
D000900:Anti-Bacterial Agents; D015306:Biogenic Monoamines; D002352:Carrier Proteins; D054848:Peptaibols; D010455:Peptides; D012097:Repressor Proteins; D029961:Zebrafish Proteins; C471725:efrapeptin C; C418489:fezf2 protein, zebrafish; D012701:Serotonin; D004298:Dopamine