ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Engrailed is required in maturing serotonin neurons to regulate the cytoarchitecture and survival of the dorsal raphe nucleus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Conserved roles of engrailed: patterning tissues and specifying cell types.Development (Cambridge, England) · 2024Review
- Engrailed transcription factors direct excitatory cerebellar neuron diversity and survival.Development (Cambridge, England) · 2024Article
- A cell atlas of the larval Aedes aegypti ventral nerve cord.Neural development · 2024Article
- Inactivation of the GATA Cofactor ZFPM1 Results in Abnormal Development of Dorsal Raphe Serotonergic Neuron Subtypes and Increased Anxiety-Like Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
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- Morphological alterations of the reticular thalamic nucleus in Engrailed-2 knockout mice.Journal of anatomy · 2020Article
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- Lmx1b is required at multiple stages to build expansive serotonergic axon architectures.eLife · 2019Article
- EZH2 Is Essential for Fate Determination in the Mammalian Isthmic Area.Frontiers in molecular neuroscience · 2019Article
- Serotonin neuron development: shaping molecular and structural identities.Wiley interdisciplinary reviews. Developmental biology · 2018Review
- Hsa-miR-27b is up-regulated in cytomegalovirus-infected human glioma cells, targets engrailed-2 and inhibits its expression.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Specific Connectivity and Unique Molecular Identity of MET Receptor Tyrosine Kinase Expressing Serotonergic Neurons in the Caudal Dorsal Raphe Nuclei.ACS chemical neuroscience · 2017Article
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- Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.Frontiers in cellular neuroscience · 2017Article
- Cellular architecture and transmitter phenotypes of neurons of the mouse median raphe region.Brain structure & function · 2017Article
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- En1 is necessary for survival of neurons in the ventral nuclei of the lateral lemniscus.Developmental neurobiology · 2016Article
- Ascending serotonin neuron diversity under two umbrellas.Brain structure & function · 2016Review
- Engrailed 1 shapes the dopaminergic and serotonergic landscape through proper isthmic organizer maintenance and function.Biology open · 2016Article
- Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Analysis of constitutive Engrailed (En) null mice previously implicated the two En homeobox paralogs in the development of serotonin (5-HT) neurons. An unresolved question is whether En plays intrinsic roles in these neurons. Here, we show that En1 and En2 are expressed in maturing 5-HT neurons that will form the dorsal raphe nucleus (DRN) and part of the median raphe nucleus. Although En1 expression in 5-HT neurons persists postnatally, En2 expression is extinguished by embryonic day 17.5. To investigate intrinsic serotonergic functions for En1/2, we generated compound conditional En mutants with floxed alleles and a cre recombinase line that becomes active in postmitotic fetal 5-HT neurons. We present evidence in support of a requirement for En1/2 in the maturation of DRN cytoarchitecture. The disruption of DRN cytoarchitecture appears to result from a defect in secondary migration of serotonergic cell bodies toward the midline rather than disruption of their primary ventral migration away from the ventricular zone. Furthermore, En1/2 are required for perinatal maintenance of serotonergic identity and postnatal forebrain 5-HT levels. Increased numbers of caspase-3-expressing cells and loss of significant numbers of 5-HT neuron cell bodies, indicative of apoptosis, occurred after loss of serotonergic identity. Analysis of an allelic series of conditional mutants showed that En1 is the predominant functional En paralog in maturing 5-HT neurons, although a small contribution from En2 was reproducibly detected. Together, our findings reveal complex intrinsic functions for En in maturing 5-HT neurons, hence necessitating a reinterpretation of their roles in 5-HT system development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.