Brain evolution by brain pathway duplication

Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits.     

The entangled history of animal and plant microRNAs

MicroRNAs (miRNAs) are small RNAs (sRNAs) that regulate gene expression in development and adaptive responses to the environment. The early days in the sRNA field was one of the most exciting and promising moments in modern biology, attracting large investments to the understanding of the underlining mechanisms and their applications, such as in gene therapy. miRNAs and other sRNAs have since been extensively studied in animals and plants, and are currently well established as an important part of most gene regulatory processes in animals and as master regulators in plants. Here, this review presents the critical discoveries and early misconceptions that shaped our current understanding of RNA silencing by miRNAs in most eukaryotes, with a focus on plant miRNAs. The presentation and language used are simple to facilitate a clear comprehension by researchers and students from various backgrounds. Hence, this is a valuable teaching tool and should also draw attention to the discovery processes themselves, such that scientists from various fields can gain insights from the successful and rapidly evolving miRNA field.     

miRNAs在肝癌干细胞中的作用

MicroRNAs (miRNAs)是一类参与转录后调控的小分子RNA,它在调控细胞的增殖、分化及肿瘤的形成等多种生理及病理过程中发挥着重要的作用.肝癌干细胞是肝癌组织中具有自我更新能力和分化潜能的一个微群体,它能够启始肝癌的发生,并且与肝癌的抗药性及复发等密切相关.已经有研究表明miRNAs对肝癌干细胞的发生发展起着重要的调控作用,包括致癌和抑癌的作用,因此总结miRNAs在肝癌干细胞中作用,有助于更好理解肝癌干细胞的特性及肝癌肿瘤生物学.近年来,除了传统的分子生物学手段,组学和系统生物学研究策略的运用也为miRNAs在肝癌中的研究提供了新的思路.鉴于此,深入研究miRNAs在肝癌干细胞中的分子机制,将为靶向肝癌干细胞的临床治疗提供新的途径.     

The molecular machines that mediate microRNA maturation

MicroRNAs (miRNA) are small RNAs that regulate the translation of thousands of message RNAs and play a profound role in mammalian biology. Over the past 5 years, significant advances have been made towards understanding the pathways that generate miRNAs and the mechanisms by which miRNAs exert their regulatory functions. An emerging theme is that miRNAs are both generated by and utilized by large and complex macromolecular assemblies. Here, we review the biology of mammalian miRNAs with a focus on the macromolecular complexes that generate and control the biogenesis of miRNAs.     

MicroRNAs in Neuronal Communication

MicroRNAs (miRNAs) are short nucleotides sequences that regulate the expression of genes in different eukaryotic cell types. A tremendous amount of knowledge on miRNAs has rapidly accumulated over the last few years, revealing the growing interest in this field of research. On the other hand, clarifying the physiological regulation of gene expression in the central nervous system is important for establishing a reference for comparison to the diseased state. It is well known that the fine tuning of neuronal networks relies on intricate molecular mechanisms, such as the adjustment of the synaptic transmission. As determined by recent studies, regulation of neuronal interactions by miRNAs has critical consequences in the development, adaptation to ambient demands, and degeneration of the nervous system. In contrast, activation of synaptic receptors triggers downstream signaling cascades that generate a vast array of effects, which includes the regulation of novel genes involved in the control of the miRNA life cycle. In this review, we have examined the hot topics on miRNA gene-regulatory activities in the broad field of neuronal communication-related processes. Furthermore, in addition to indicating the newly described effect of miRNAs on the regulation of specific neurotransmitter systems, we have pointed out how these systems affect the expression, transport, and stability of miRNAs. Moreover, we discuss newly described and under-investigation mechanisms involving the intercellular transfer of miRNAs, aided by exosomes and gap junctions. Thus, in the current review, we were able to highlight recent findings related to miRNAs that indisputably contributed towards the understanding of the nervous system in health and disease.     

Retrotransposons and piRNA: The missing link in central nervous system

From times when the whole genome were not available to the present explosion of genome knowledge, the biology of non-coding RNA molecules are an unknown ocean of gems. One among them are PIWI-interacting RNAs (piRNAs) that restrict the mobility of various retrotransposons. PIWI proteins and piRNAs once thought to be germline specific was now explored to be expressed in different somatic cells. Emerging proofs of piRNAs from central nervous system has raised serious questions regarding the role of retrotransposons and its silencing mechanism. In this review, we have focused on the existing knowledge of retrotransposons and piRNAs in the central nervous system and have provided future insights. Meta-analysis of retrotransposons in various mammalian genomes and piRNA targets showcased the abundance of LINE transposon and the possibility of piRNA mediated retrotransposon expression. Thus, understanding the retrotransposons-piRNA pathway will provide a new vision for the study of development, physiology and pathology of the central nervous system.     

Considering the zebrafish in a comparative context

This article introduces a special issue on zebrafish biology that attempts to integrate developmental genetics with comparative studies of other fish species. For zebrafish researchers, comparative work offers a better understanding of the evolutionary history of their model system. Comparative biologists can gain many insights from the developmental and genetic mechanisms revealed in zebrafish that have contributed to the huge range of morphological variation among fishes that has arisen over millions of years. These ideas are considered here in various contexts, including systematics, genome organization and the development of the nervous system, pigmentation, craniofacial skeleton and dentition. Studies of the zebrafish in phylogenetic context provide an opportunity for synergy between communities using these two fundamentally different approaches.     

Control of neural crest cell behavior and migration

Neural crest cells (NCCs) are a remarkable, dynamic group of cells that travel long distances in the embryo to reach their target sites. They are responsible for the formation of craniofacial bones and cartilage, neurons and glia in the peripheral nervous system, and pigment cells. Live imaging of NCCs as they traverse the embryo has been critical to increasing our knowledge of their biology. NCCs exhibit multiple behaviors and communicate with each other and their environment along each step of their journey. Imaging combined with molecular manipulations has led to insights into the mechanisms controlling these behaviors. In this review, we highlight studies that have used live imaging to provide novel insight into NCC migration and discuss how continued use of such techniques can advance our understanding of NCC biology.     

MicroRNAs Involved in Skeletal Muscle Differentiation

MicroRNAs (miRNAs) negatively regulate gene expression by promoting degradation of target mRNAs or inhibiting their translation. Previous studies have expanded our understanding that miRNAs play an important role in myogenesis and have a big impact on muscle mass, muscle fiber type and muscle-related diseases. The muscle-specific miRNAs, miR-206, miR-1 and miR-133, are among the most studied and best characterized miRNAs in skeletal muscle differentiation. They have a profound influence on multiple muscle differ-entiation processes, such as alternative splicing, DNA synthesis, and cell apoptosis. Many non-muscle-specific miRNAs are also required for the differentiation of muscle through interaction with myogenic factors. Studying the regulatory mechanisms of these miRNAs in muscle differentiation will extend our knowledge of miRNAs in muscle biology and will improve our understanding of the myogenesis regulation.     

microRNAs as Developmental Regulators

The field of miRNA biology is relatively young, but its impact on our understanding of the regulation of a wide array of cell functions is far-reaching. The importance of miRNAs in development has become nearly ubiquitous, with miRNAs contributing to development of most cells and organs. Although miRNAs are clearly interwoven into known regulatory networks that control cell development, the specific modalities by which they intersect are often quite distinct and cleverly achieved. The frequently emerging theme of feed-back and feed-forward loops to either counterbalance or reinforce the gene programs that they influence is a common thread. Many of these examples of miRNAs as developmental regulators are presently found in organs with different miRNAs and targets, whereas novel, unexpected themes emerge in the context of mouse development as we learn more about this rapidly developing area of biology.     

Computational identification of miRNAs,their targets and functions in three‐spined stickleback (Gasterosteus aculeatus)

An intriguing question in biology is how the evolution of gene regulation is shaped by natural selection in natural populations. Among the many known regulatory mechanisms, regulation of gene expression by microRNAs (miRNAs) is of critical importance. However, our understanding of their evolution in natural populations is limited. Studying the role of miRNAs in three‐spined stickleback, an important natural model for speciation research, may provide new insights into adaptive polymorphisms. However, lack of annotation of miRNA genes in its genome is a bottleneck. To fill this research gap, we used the genome of three‐spined stickleback to predict miRNAs and their targets. We predicted 1486 mature miRNAs using the homology‐based miRNA prediction approach. We then performed functional annotation and enrichment analysis of these targets, which identified over‐represented motifs. Further, a database resource (GAmiRdb) has been developed for dynamically searching miRNAs and their targets exclusively in three‐spined stickleback. Finally, the database was used in two case studies focusing on freshwater adaptation in natural populations. In the first study, we found 44 genomic regions overlapping with predicted miRNA targets. In the second study, we identified two SNPs altering the MRE seed site of sperm‐specific glyceraldehyde‐3‐phosphate gene. These findings highlight the importance of the GAmiRdb knowledge base in understanding adaptive evolution.     

The control of neural stem cells by morphogenic signals

A complex orchestration of stem-cell specification, expansion and differentiation is required for the proper development of the nervous system. Although progress has been made on the role of individual genes in each of these processes, there are still unresolved questions about how gene function translates to the dynamic assembly of cells into tissues. Recently, stem-cell biology has emerged as a bridge between the traditional fields of cell biology and developmental genetics. In addition to their potential therapeutic role, stem cells are being exploited as experimental 'logic chips' that integrate information and exhibit self-organizing properties. Recent studies provide new insights on how morphogenic signals coordinate major stem cell decisions to regulate the size, shape and cellular diversity of the nervous system.     

Larval neurogenesis in Sabellaria alveolata reveals plasticity in polychaete neural patterning

The investigation of neurogenesis in polychaetes not only facilitates insights into the developmental biology of this group, but also provides new data for phylogenetic analyses. This should eventually lead toward a better understanding of metazoan evolution including key issues such as the ontogenetic processes that underlie body segmentation. We here document the development of the larval nervous system in the polychaete Sabellaria alveolata using fluorescence-coupled antibodies directed against serotonin, FMRFamide, and tubulin in combination with confocal laser scanning microscopy and 3D reconstruction software. The overall pattern of neurogenesis in S. alveolata resembles the condition found in other planktonic polychaete trochophores where the larval neural body plan including a serotonergic prototroch nerve ring is directly followed by adult features of the nervous system such as circumesophageal connectives and paired ventral nerve cords. However, distinct features are also found in S. alveolata, such as the innervation of the apical organ with ring-shaped neurons, the low number of immunoreactive perikarya, and the lack of a posterior serotonergic cell. Moreover, in the larvae of S. alveolata, two distinct modes of neuronal development are expressed, viz. the simultaneous formation of the first three segmental neurons of the peripheral nervous system on the one hand versus the sequential appearance of the ventral commissures on the other. This highlights the complex mechanisms that underlie annelid body segmentation and indicates divergent developmental pathways within polychaete annelids that lead to the segmented nervous system of the adult.     

Emerging roles of microRNAs in the control of embryonic stem cells and the generation of induced pluripotent stem cells

MicroRNAs (miRNAs) have emerged as critical regulators of gene expression. These small, non-coding RNAs are believed to regulate more than a third of all protein coding genes, and they have been implicated in the control of virtually all biological processes, including the biology of stem cells. The essential roles of miRNAs in the control of pluripotent stem cells were clearly established by the finding that embryonic stem (ES) cells lacking proteins required for miRNA biogenesis exhibit defects in proliferation and differentiation. Subsequently, the function of numerous miRNAs has been shown to control the fate of ES cells and to directly influence critical gene regulatory networks controlled by pluripotency factors Sox2, Oct4, and Nanog. Moreover, a growing list of tissue-specific miRNAs, which are silenced or not processed fully in ES cells, has been found to promote differentiation upon their expression and proper processing. The importance of miRNAs for ES cells is further indicated by the exciting discovery that specific miRNA mimics or miRNA inhibitors promote the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Although some progress has been made during the past two years in our understanding of the contribution of specific miRNAs during reprogramming, further progress is needed since it is highly likely that miRNAs play even wider roles in the generation of iPS cells than currently appreciated. This review examines recent developments related to the roles of miRNAs in the biology of pluripotent stem cells. In addition, we posit that more than a dozen additional miRNAs are excellent candidates for influencing the generation of iPS cells as well as for providing new insights into the process of reprogramming.     

Exploring the role of microRNAs in axolotl regeneration

The axolotl, Ambystoma mexicanum, is used extensively for research in developmental biology, particularly for its ability to regenerate and restore lost organs, including in the nervous system, to full functionality. Regeneration in mammals typically depends on the healing process and scar formation with limited replacement of lost tissue. Other organisms, such as spiny mice (Acomys cahirinus), salamanders, and zebrafish, are able to regenerate some damaged body components. Blastema is a tissue that is formed after tissue injury in such organisms and is composed of progenitor cells or dedifferentiated cells that differentiate into various cell types during regeneration. Thus, identifying the molecules responsible for initiation of blastema formation is an important aspect for understanding regeneration. Introns, a major source of noncoding RNAs (ncRNAs), have characteristic sizes in the axolotl, particularly in genes associated with development. These ncRNAs, particularly microRNAs (miRNAs), exhibit dynamic regulation during regeneration. These miRNAs play an essential role in timing and control of gene expression to order and organize processes necessary for blastema creation. Master keys or molecules that underlie the remarkable regenerative abilities of the axolotl remain to be fully explored and exploited. Further and ongoing research on regeneration promises new knowledge that may allow improved repair and renewal of human tissues.     

长链非编码RNA在血液系统肿瘤中作用的研究进展

随着分子生物学技术的飞速发展,人们对于长链非编码RNA(Long non-coding RNA,lncRNA)的研究越来越深入。lncRNA不仅在生物体正常生物活动中不可或缺,还在许多疾病尤其是肿瘤中扮演重要角色。已有的研究表明多种lncRNA与血液系统肿瘤密切相关,具有影响抑癌基因p15表达、p53蛋白功能,以及与miRNA相互作用参与疾病等功能。本文综述了血液系统肿瘤相关的lncRNA并着重介绍与p15、p53、miRNA有关的lncRNA以及它们的相互作用在疾病中发挥的功能,以期能够全面了解血液系统肿瘤相关lncRNA的作用特点,为血液系统肿瘤的研究、诊断以及治疗提供新的思路。