The role of Zic transcription factors in regulating hindbrain retinoic acid signaling.
BACKGROUND
The reiterated architecture of cranial motor neurons aligns with the segmented structure of the embryonic vertebrate hindbrain. Anterior-posterior identity of cranial motor neurons depends, in part, on retinoic acid signaling levels. The early vertebrate embryo maintains a balance between retinoic acid synthetic and degradative zones on the basis of reciprocal expression domains of the retinoic acid synthesis gene aldhehyde dehydrogenase 1a2 (aldh1a2) posteriorly and the oxidative gene cytochrome p450 type 26a1 (cyp26a1) in the forebrain, midbrain, and anterior hindbrain.


RESULTS
This manuscript investigates the role of zinc finger of the cerebellum (zic) transcription factors in regulating levels of retinoic acid and differentiation of cranial motor neurons. Depletion of zebrafish Zic2a and Zic2b results in a strong downregulation of aldh1a2 expression and a concomitant reduction in activity of a retinoid-dependent transgene. The vagal motor neuron phenotype caused by loss of Zic2a/2b mimics a depletion of Aldh1a2 and is rescued by exogenously supplied retinoic acid.


CONCLUSIONS
Zic transcription factors function in patterning hindbrain motor neurons through their regulation of embryonic retinoic acid signaling.
Department of Biological Sciences, University of Alberta, CW405, Edmonton, AB T6G 2E9, Canada.
Danna L
DL
Drummond
Caroline S
CS
Cheng
Lyndsay G
LG
Selland
Jennifer C
JC
Hocking
Lisa B
LB
Prichard
Andrew J
AJ
Waskiewicz
D000080924:Aldehyde Dehydrogenase 1 Family; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D012249:Rhombencephalon / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism; D029961:Zebrafish Proteins
D014157:Transcription Factors; C492123:ZIC1 protein, human; D029961:Zebrafish Proteins; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; C000607085:cyp26a1 protein, zebrafish; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase