Developmental Neurobiology最新文献

Myelination of axons in the neonatal brain is a highly complex process primarily achieved by oligodendroglial cells (OLs). OLs express receptors for γ-aminobutyric acid (GABA) which is released from cortical interneurons on a basal level, while glial cells can be a source of GABA, too. We investigated GABA-induced oligodendroglial maturation, proliferation, apoptosis, and myelin production after pharmacological inhibition of GABA_A and GABA_B in the neonatal rat brain. Daily injections of the reverse GABA_A receptor agonist (DMCM) and the GABA_B receptor antagonist (CGP35348) were performed from postnatal day 6 (P6) to P11. MBP expression was examined by Western blots and immunohistochemistry. Furthermore, we determined the number of CC1⁺OLIG2⁺ and CNP⁺OLIG2⁺ cells to assess maturation, the number of PCNA⁺OLIG2⁺ oligodendrocytes to assess proliferation, the number of oligodendrocyte precursor cells (PDGFRα⁺OLIG2⁺), and apoptosis of OLs (CASP3A⁺OLIG2⁺) as well as apoptotic cells in total (CASP3A⁺DAPI⁺) at P11 and P15. In addition, we analyzed the expression Pdgfrα and CNP. MBP expression was significantly reduced after CGP treatment at P15. In the same animal group, CNP expression and CNP⁺OLIG2⁺ cells decreased temporarily at P11. At P15, the proliferation of PCNA⁺OLIG2⁺ cells and the number of PDGFRα⁺OLIG2⁺ cells increased after GABA_B receptor antagonization whereas no significant differences were visible in the Pdgfrα gene expression. No changes in apoptotic cell death were observed. CGP treatment induced a transient maturational delay at P11 and deficits in myelin expression at P15 with increased oligodendroglial proliferation. Our in vivo study indicates GABA_B receptor activity as a potential modulator of oligodendroglial development.

Like human language, song in songbirds is learned during an early sensitive period and is facilitated by motivation to seek out social interactions with vocalizing adults. Songbirds are therefore powerful models with which to understand the neural underpinnings of vocal learning. Social motivation and early social orienting are thought to be mediated by the oxytocin system; however, the developmental trajectory of oxytocin receptors in songbirds, particularly as it relates to song learning, is currently unknown. This gap in knowledge has hindered the development of songbirds as a model of the role of social orienting in vocal learning. In this study, we used quantitative PCR to measure oxytocin receptor expression during the sensitive period of song learning in zebra finches (Taeniopygia guttata). We focused on brain regions important for social motivation, attachment, song recognition, and song learning. We detected expression in these regions in both sexes from posthatch day 5 to adulthood, encompassing the entire period of song learning. In this species, only males sing; we found that in regions implicated in song learning specifically, oxytocin receptor mRNA expression was higher in males than females. These sex differences were largest during the developmental phase when males attend to and memorize tutor song, suggesting a functional role of expression in learning. Our results show that oxytocin receptors are expressed in relevant brain regions during song learning, and thus provide a foundation for developing the zebra finch as a model for understanding the mechanisms underlying the role of social motivation in vocal development.

Nervous system development has been intensely studied in insects (especially Drosophila melanogaster), providing detailed insights into the genetic regulatory network governing the formation and maintenance of the neural stem cells (neuroblasts) and the differentiation of their progeny. Despite notable advances over the last two decades, neurogenesis in other arthropod groups remains by comparison less well understood, hampering finer resolution of evolutionary cell type transformations and changes in the genetic regulatory network in some branches of the arthropod tree of life. Although the neurogenic cellular machinery in malacostracan crustaceans is well described morphologically, its genetic molecular characterization is pending. To address this, we established an in situ hybridization protocol for the crayfish Procambarus virginalis and studied embryonic expression patterns of a suite of key genes, encompassing three SoxB group transcription factors, two achaete–scute homologs, a Snail family member, the differentiation determinants Prospero and Brain tumor, and the neuron marker Elav. We document cell type expression patterns with notable similarities to insects and branchiopod crustaceans, lending further support to the homology of hexapod–crustacean neuroblasts and their cell lineages. Remarkably, in the crayfish head region, cell emigration from the neuroectoderm coupled with gene expression data points to a neuroblast-independent initial phase of brain neurogenesis. Further, SoxB group expression patterns suggest an involvement of Dichaete in segmentation, in concordance with insects. Our target gene set is a promising starting point for further embryonic studies, as well as for the molecular genetic characterization of subregions and cell types in the neurogenic systems in the adult crayfish brain.

Precise cochlear neuronal development is vital to hearing ability. Understanding the developmental process of the spiral ganglion is useful for studying hearing loss aimed at aging or regenerative therapy. Although interspecies differences have been reported between rodents and humans, to date, most of our knowledge about the development of cochlear neuronal development has been obtained from rodent models because of the difficulty in using human fetal samples in this field. In this study, we investigated cochlear neuronal development in a small New World monkey species, the common marmoset (Callithrix jacchus). We examined more than 25 genes involved in the neuronal development of the cochlea and described the critical developmental steps of these neurons. We also revealed similarities and differences between previously reported rodent models and this primate animal model. Our results clarified that this animal model of cochlear neuronal development is more similar to humans than rodents and is suitable as an alternative for the analysis of human cochlear development. The time course established in this report will be a useful tool for studying primate-specific neuronal biology of the inner ear, which could eventually lead to new treatment strategies for human hearing loss.

The transcription factors Olig2 and Sox10 jointly define oligodendroglial identity. Because of their continuous presence during development and in the differentiated state they shape the oligodendroglial regulatory network at all times. In this review, we exploit their eminent role and omnipresence to elaborate the central principles that organize the gene regulatory network in oligodendrocytes in such a way that it preserves its identity, but at the same time allows defined and stimulus-dependent changes that result in an ordered lineage progression, differentiation, and myelination. For this purpose, we outline the multiple functional and physical interactions and intricate cross-regulatory relationships with other transcription factors, such as Hes5, Id, and SoxD proteins, in oligodendrocyte precursors and Tcf7l2, Sip1, Nkx2.2, Zfp24, and Myrf during differentiation and myelination, and interpret them in the context of the regulatory network.

Glia are widely distributed in the central nervous system and are closely related to cell metabolism, signal transduction, support, cell migration, and other nervous system development processes and functions. Glial development is complex and essential, including the processes of proliferation, differentiation, and migration, and requires precise regulatory networks. Noncoding RNAs (ncRNAs) can be deeply involved in glial development through gene regulation. Here, we review the regulatory roles of ncRNAs in glial development. We briefly describe the classification and functions of noncoding RNAs and focus on microRNAs (miRNAs) and long ncRNAs (lncRNAs), which have been reported to participate extensively during glial formation. The highlight of this summary is that miRNAs and lncRNAs can participate in and regulate the signaling pathways of glial development. The review not only describes how noncoding RNAs participate in nervous system development but also explains the processes of glial development, providing a foundation for subsequent studies on glial development and new insights into the pathogeneses of related neurological diseases.

Early-life stress (ELS) is considered a relevant etiological factor for neurodegenerative and mental disorders. In the present study, we hypothesized that ELS may persistently and sex dependently influence blood–brain barrier (BBB) integrity and function during critical periods of brain development and consequently determine susceptibility to and sex-related prevalence of chronic diseases in adult life. We used the maternal separation (MS) procedure in rats to model ELS and evaluated BBB permeability and gene expression of selected tight junction (TJ) proteins, glucose transporter type 1 (Slc2a1) and aquaporin 4 (Aqp4) in the medial prefrontal cortex (mPFC), dorsal striatum (dSTR) and hippocampus of juvenile and adult rats. Serum concentrations of a peripheral marker of BBB function (S100β) and proinflammatory cytokines were also assessed. We observed developmental sealing of the BBB and sex differences in the permeability of the BBB and the mRNA expression of TJ proteins and Slc2a1. Adult females showed lower BBB permeability and higher levels of Cldn3, Cldn5, Ocln, and Slc2a1 in the mPFC and dSTR than males. MS temporarily increased BBB permeability in the dSTR of juvenile males and affected mRNA expression of the majority of studied proteins related to BBB function in age-, region- and sex-dependent manners. Additionally, MS sex dependently decreased serum S100β levels and did not affect proinflammatory cytokine concentrations. In general, our study did not reveal a clear or strong negative effect of MS on BBB integrity. However, the results suggest that ELS may induce adaptive/maladaptive changes or compensatory mechanisms within the BBB of unknown yet consequences.

The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to women at risk for preterm birth during a critical period of fetal development for mesocortical pathways. Yet, little information is available regarding the potential effects of 17-OHPC on the developing fetal brain. In rat models, the mesocortical serotonin pathway is sensitive to progestins. Progesterone receptor (PR) is expressed in layer 3 pyramidal neurons of medial prefrontal cortex (mPFC) and in serotonergic neurons of the dorsal raphe. The present study tested the hypothesis that exposure to 17-OHPC during development disrupts serotonergic innervation of the mPFC in adolescence and impairs behavior mediated by this pathway in adulthood. Administration of 17-OHPC from postnatal days 1–14 decreased the density of SERT-ir fibers within superficial and deep layers and decreased the density of synaptophysin-ir boutons in all layers of prelimbic mPFC at postnatal day 28. In addition, rats exposed to 17-OHPC during development were less likely to make impulsive choices in the Delay Discounting task, choosing the larger, delayed reward more often than controls at moderate delay times. Interestingly, 17-OHPC exposed rats were more likely to fail to make any choice (i.e., increased omissions) compared to controls at longer delays, suggesting disruptions in decision-making. These results suggest that further investigation is warranted in the clinical use of 17-OHPC to better inform a risk/benefit analysis of progestin use in pregnancy.

The avian basilar papilla is a valuable model system for exploring the developmental determination and differentiation of sensory hair cells and their innervation. In the mature basilar papilla, hair cells form a well-known continuum between two extreme types—tall and short hair cells—that differ strikingly in their innervation. Previous work identified Wnt9a as a crucial factor in this differentiation. Here, we quantified the number and volume of immunolabelled presynaptic ribbons in tall and short hair cells of chickens, from developmental stages shortly after ribbons first appear to the mature posthatching condition. Two longitudinal locations were sampled, responding to best frequencies of approximately 1 kHz and approximately 5.5 kHz when mature. We found significant reductions of ribbon number during normal development in the tall-hair-cell domains, but stable, low numbers in the short-hair-cell domains. Exposing developing hair cells to continuous, excessive Wnt9a levels (through virus-mediated overexpression) led to transiently abnormal high numbers of ribbons and a delayed reduction of ribbon numbers at all sampled locations. Thus, (normally) short-hair-cell domains also showed tall-hair-cell like behaviour, confirming previous findings (Munnamalai et al., 2017). However, at 3 weeks posthatching, ribbon numbers had decreased to the location-specific typical values of control hair cells at all sampled locations. Furthermore, as shown previously, mature hair cells at the basal, high-frequency location harboured larger ribbons than more apically located hair cells. This was true for both normal and Wnt9a-overexposed basilar papillae.