Analysis of transcriptional codes for zebrafish dopaminergic neurons reveals essential functions of Arx and Isl1 in prethalamic dopaminergic neuron development.
Distinct groups of dopaminergic neurons develop at defined anatomical sites in the brain to modulate function of a large diversity of local and far-ranging circuits. However, the molecular identity as judged from transcription factor expression has not been determined for all dopaminergic groups. Here, we analyze regional expression of transcription factors in the larval zebrafish brain to determine co-expression with the Tyrosine hydroxylase marker in dopaminergic neurons. We define sets of transcription factors that clearly identify each dopaminergic group. These data confirm postulated relations to dopaminergic groups defined for mammalian systems. We focus our functional analysis on prethalamic dopaminergic neurons, which co-express the transcription factors Arx and Isl1. Morpholino-based knockdown reveals that both Arx and Isl1 are strictly required for prethalamic dopaminergic neuron development and appear to act in parallel. We further show that Arx contributes to patterning in the prethalamic region, while Isl1 is required for differentiation of prethalamic dopaminergic neurons.
Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
Alida
A
Filippi
Chamaiphorn
C
Jainok
Wolfgang
W
Driever
D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D002395:Catecholamines / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060172:Morpholinos / Q000494:pharmacology; D011301:Preoptic Area / Q000166:cytology / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism; D013788:Thalamus / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D002395:Catecholamines; D060850:LIM-Homeodomain Proteins; D060172:Morpholinos; D014157:Transcription Factors; D029961:Zebrafish Proteins; C575642:arxa protein, zebrafish; C063843:insulin gene enhancer binding protein Isl-1; C515950:orthopedia protein, zebrafish