SHH and FGF8 play distinct roles during development of noradrenergic neurons in the locus coeruleus of the zebrafish.
Several signaling pathways have been implicated in the development of dopaminergic and serotonergic neurons. Here, we analyzed the formation of noradrenergic (NAergic) cells in the locus coeruleus (LC) of zebrafish. In the sonic hedgehog (shh) mutant, cells positive for tyrosine hydroxylase, a marker for putative NAergic cells in the LC were reduced. Similarly, the inhibition of translation of all hh genes and the perturbation of Shh signaling by forskolin resulted in a decrease in the number of cells. Conversely, when SHH was overexpressed, an increase in number was observed. Thus, Shh is involved in maintaining the appropriate number of cells in the LC. While elevated levels of bone morphogenetic protein 4 (BMP4) did not attenuate tyrosine hydroxylase-positive cells, exogenous fibroblast growth factor 8 (FGF8) rescued NAergic neurons in the acerebellar (ace) mutant, providing direct in vivo evidence that Fgf8 is required for the induction of NAergic neurons in the LC.
Institute of Molecular and Cell Biology, National University of Singapore, Singapore, Republic of Singapore.
Chen Sok
CS
Lam
Inna
I
Sleptsova-Friedrich
Angus D
AD
Munro
Vladimir
V
Korzh
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D052005:Bone Morphogenetic Protein Receptors, Type I; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000172:deficiency* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053823:Hedgehog Proteins; D008125:Locus Coeruleus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017978:Receptors, Growth Factor; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
D053823:Hedgehog Proteins; D011500:Protein Synthesis Inhibitors; D017978:Receptors, Growth Factor; D015534:Trans-Activators; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I; D009638:Norepinephrine