RRC ID 40020
著者 Love CE, Prince VE.
タイトル Rest represses maturation within migrating facial branchiomotor neurons.
ジャーナル Dev Biol
Abstract The vertebrate brain arises from the complex organization of millions of neurons. Neurogenesis encompasses not only cell fate specification from neural stem cells, but also the terminal molecular and morphological maturation of neurons at correct positions within the brain. RE1-silencing transcription factor (Rest) is expressed in non-neural tissues and neuronal progenitors where it inhibits the terminal maturation of neurons by repressing hundreds of neuron-specific genes. Here we show that Rest repression of maturation is intimately linked with the migratory capability of zebrafish facial branchiomotor neurons (FBMNs), which undergo a characteristic tangential migration from hindbrain rhombomere (r) 4 to r6/r7 during development. We establish that FBMN migration is increasingly disrupted as Rest is depleted in zebrafish rest mutant embryos, such that around two-thirds of FBMNs fail to complete migration in mutants depleted of both maternal and zygotic Rest. Although Rest is broadly expressed, we show that de-repression or activation of Rest target genes only within FBMNs is sufficient to disrupt their migration. We demonstrate that this migration defect is due to precocious maturation of FBMNs, based on both morphological and molecular criteria. We further show that the Rest target gene and alternative splicing factor srrm4 is a key downstream regulator of maturation; Srrm4 knockdown partially restores the ability of FBMNs to migrate in rest mutants while preventing their precocious morphological maturation. Rest must localize to the nucleus to repress its targets, and its subcellular localization is highly regulated: we show that targeting Rest specifically to FBMN nuclei rescues FBMN migration in Rest-deficient embryos. We conclude that Rest functions in FBMN nuclei to inhibit maturation until the neurons complete their migration.
巻・号 401(2)
ページ 220-35
公開日 2015-5-15
DOI 10.1016/j.ydbio.2015.02.021
PII S0012-1606(15)00093-7
PMID 25769695
PMC PMC4424086
MeSH Animals Animals, Genetically Modified Cell Movement / physiology Cell Nucleus / genetics Facial Nerve / cytology Facial Nerve / metabolism* Gene Knockdown Techniques Morpholinos / genetics Motor Neurons / metabolism* Nerve Tissue Proteins / genetics Neural Stem Cells / metabolism* Neurogenesis / genetics* Repressor Proteins / biosynthesis Repressor Proteins / genetics* Rhombencephalon / embryology Zebrafish Zebrafish Proteins / genetics
IF 2.896
引用数 3
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
ゼブラフィッシュ Tg(isl1:GFP)/rw0