Engrailed genes control developmental fate of serotonergic and noradrenergic neurons in mid- and hindbrain in a gene dose-dependent manner.
In vertebrates and insects, the homeobox transcription factors of the engrailed family have a dual function. They take part in regionalization during early embryogenesis and later in neuronal specification. In mammals, two engrailed homologues exist, engrailed-1 and engrailed-2, which are expressed in a broad band around the isthmus at an age when the serotonergic and noradrenergic neurons in mid/hindbrain are generated. The analysis of engrailed-1 and -2 double mutant mice revealed a specific, redundant, and gene dose-dependent requirement of the two transcription factors for the development of the serotonergic dorsal raphe nucleus and the noradrenergic locus caeruleus. Both nuclei are lost in engrailed double mutant mice; however, directly adjacent nuclei of the same neurotransmitter phenotype are not affected. An almost identical phenotype is found in mutant mice null for Wnt1, indicating that the engrailed genes provide essential positional information for the development of the two nuclei during early embryogenesis.
Simon
Horst H
HH
Interdisciplinary Center for Neuroscience, Department of Neuroanatomy, University of Heidelberg, 69120 Heidelberg, Germany. horst.simon@urz.uni-heidelberg.de
Scholz
Christian
C
O'Leary
Dennis D M
DD
D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008125:Locus Coeruleus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010641:Phenotype; D011903:Raphe Nuclei / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D051153:Wnt Proteins; D051155:Wnt1 Protein; D000099266:Engrailed 2 Protein
D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009638:Norepinephrine; D012701:Serotonin; D051153:Wnt Proteins; D051155:Wnt1 Protein; D000099266:Engrailed 2 Protein; C080330:En1 protein, mouse; C495246:Wnt1 protein, mouse