Cover image for Vol. 38 Issue 9

Edited By: Andrew Moore

Online ISSN: 1521-1878



From novel insights into neurodegenerative diseases to understanding the structural basis of memory formation, this special collection covers an broad range of papers from basic research through to biomedicine. We hope you enjoy reading them.

For primer literature of relevance to the articles below, see the Encyclopedia of Life SciencesELS_Logo entries under Neuroscience.

The vertebrate Hox gene regulatory network for hindbrain segmentation: Evolution and diversification
Hugo J. Parker, Marianne E. Bronner and Robb Krumlauf, BioEssays, Volume 38, Issue 6, June 2016, pages 526-538.
DOI: 10.1002/bies.201600010

A developmental gene regulatory network couples Hox gene expression to hindbrain segmentation in all vertebrates. Evidence from jawless vertebrates and invertebrate chordates indicates that this pan-vertebrate network originated from an ancient anterior–posterior patterning program. Cross-species comparisons suggest diversification in the network may contribute to neuro-anatomical differences between vertebrates.

Why direct effects of predation complicate the social brain hypothesis
Wouter van der Bijl, Niclas Kolm, BioEssays, Volume 38, Issue 6, June 2016, pages 568-577.
DOI: 10.1002/bies.201500166

Correlations between sociality and brain size have been hypothesized to stem from a causal link. But additional correlations of both variables with predation provide an alternative explanation. What are the evolutionary forces behind the evolution of large brains?

Making sense of the sensory regulation of hunger neurons
Yiming Chen and Zachary A. Knight, BioEssays, Volume 38, Issue 4, April 2016, pages 316-324.
DOI: 10.1002/bies.201500167

Recent experiments using fiber photometry, microendoscope-based calcium imaging, and optrode recordings have revealed that arcuate hunger neurons are rapidly modulated by the sensory detection of food. This essay discusses the possible function of this unexpected modulation, including the role of motivation and reinforcement, cephalic phase responses, and anticipatory.

Genomic divergence and brain evolution: How regulatory DNA influences development of the cerebral cortex
Debra L. Silver, BioEssays, Volume 38, Issue 2, February 2016, pages 162-171.
DOI: 10.1002/bies.201500108

corticogenesis;enhancer;evolution;neocortex;stem cell

Gene expression differences distinguish our brains from those of non-human primates. This review discusses these differences with an emphasis on non-coding regulatory DNA changes relevant for the cerebral cortex.

Alzheimer's in 3D culture: Challenges and perspectives
Carla D'Avanzo, Jenna Aronson, Young Hye Kim, Se Hoon Choi, Rudolph E. Tanzi and Doo Yeon Kim, BioEssays, Volume 37, Issue 10, October 2015, pages 1139-1148.
DOI: 10.1002/bies.201500063

3D culture, Alzheimer's disease, APP, human stem cell, presenelin

Recently, we recapitulated key events of Alzheimer's disease pathogenesis in a 3D human stem cells culture system. This model enhances beta-amyloid accumulation and neurofibrillary tau tangles (NFT), providing a powerful cellular model for Alzheimer's disease. In this review, we discuss the current progress of modeling neurodegenerative diseases in 3D cultures.

Axonal wiring in neural development: Target-independent mechanisms help to establish precision and complexity
Milan Petrovic and Dietmar Schmucker, BioEssays, Volume 37, Issue 9, September 2015, pages 996-1004.
DOI: 10.1002/bies.201400222

axonal branching, axonal tiling, axon-axon interactions, axon guidance, cell recognition molecules, chemoaffinity, neural development, sensory maps, target-independent wiring

A diverse set of target-independent neuronal wiring mechanisms are essential for neuronal circuit development. These mechanisms include the spatial patterning of axonal growth cones, afferent axon–axon interactions and cell-intrinsic regulatory programs, which autonomously instruct axonal guidance, axon branching, and synaptic targeting independent of cues from the target region.

Significance of transcytosis in Alzheimer's disease: BACE1 takes the scenic route to axons
Virginie Buggia-Prévot and Gopal Thinakaran, BioEssays, Volume 37, Issue 8, August 2015, pages 888–898.
DOI: 10.1002/bies.201500019

Alzheimer's disease, amyloid peptide, BACE1, endosomes, neronal transport, protein trafficking, transcytosis

Trafficking dysfunction contributes to pathogenesis in Alzheimer's disease and other neurodegenerative diseases. In neurons, BACE1 undergoes dendrite-to-axon transcytosis. Notably, BACE1 internalized in dendrites undergoes unidirectional retrograde transport. The regulation of BACE1 dynamic transport and transcytosis has significant implications for Alzheimer's disease ß-amyloid production and BACE1 cleavage of other neuronal substrates.

Neuronal hyperactivity – A key defect in Alzheimer's disease?
Marc Aurel Busche and Arthur Konnerth, BioEssays, Volume 37, Issue 6, June 2015, pages 624-632.
DOI: 10.1002/bies.201500004

Alzheimer's disease, amyloid-ß, biomedicine, brain imaging, mouse models, neuronal dysfunction, neuronal hyperactivity

The functional impairments of brain neurons in Alzheimer's disease are not entirely clear. While early studies emphasized the relevance of a gradual reduction in neuronal activity, there is now accumulating data, both in humans and animal models, revealing the pathophysiological importance of hyperactivity in the diseased brain.

Molecular signaling mechanisms of axon-glia communication in the peripheral nervous system
Tamara Grigoryan and Walter Birchmeier, BioEssays, Volume 37, Issue 5, May 2015, pages 502-513.
DOI: 10.1002/bies.201400172

glia, myelination, paracrine mechanism, Wnt

Complex communication mechanisms between neurons and Schwann cells safeguard proper development and function of the entire peripheral nervous system. We provide insights into the molecular systems that signal between neuronal projections – axons, Schwann cells and their extracellular environment, focusing on data obtained from in vivo genetically modified mouse models.

Mechanical systems biology of C. elegans touch sensation
Michael Krieg, Alexander R. Dunn and Miriam B. Goodman, BioEssays, Volume 37, Issue 3, March 2015, pages 335-344.
DOI: 10.1002/bies.201400154

Caenorhabditis elegans, cytoskeleton, force transmission, mechanics, mechanosensation, tension, touch

Before our fingertips feel a touch, it is transmitted from an acellular layer of the skin through the dermis and cytoskeletal elements in the sensory cell, where a mechanoelectrical transduction channel converts the mechanical stimulus into an electrical response. Whereas the individual MeT channels that govern the signal conversion are different in nematodes and mammals, the transmission pathway and the underlying physics are likely to be conserved.

Golgi defects enhance APP amyloidogenic processing in Alzheimer's disease
Gunjan Joshi and Yanzhuang Wang, BioEssays, Volume 37, Issue 3, March 2015, pages 240-247.
DOI: 10.1002/bies.201400116

Alzheimer's disease, amyloid beta, amyloid precursor protein, Golgi defects, GRASP55, GRASP65, neuronal function

The Golgi structure is maintained by Golgi structural proteins such as GRASP65. In Alzheimer's disease, Aß accumulation activates Cdk5 that phosphorylates GRASP65 and causes Golgi fragmentation. Subsequently, Golgi fragmentation not only enhances APP trafficking and Aß production, but also impacts trafficking and processing of many other essential neuronal proteins.

Atlas stumbled: Kinesin light chain-1 variant E triggers a vicious cycle of axonal transport disruption and amyloid-ß generation in Alzheimer's disease
Kathlyn J. Gan, Takashi Morihara and Michael A. Silverman, BioEssays, Volume 37, Issue 2, February 2015, pages 131-141.
DOI: 10.1002/bies.201400131

alternative splicing, Alzheimer's disease, amyloid-beta, amyloid precursor protein, axonal transport, kinesin, kinesin light chain

In Alzheimer's disease (AD), it is controversial whether transport defects cause or arise from amyloid-ß (Aß)-induced toxicity. Kinesin light chain-1 splice variant E (KLC1vE) modifies Aß accumulation, supporting a causal role. Here, we hypothesize how KLC1vE-induced transport defects drive Aß generation, kinase dysregulation, and global transport impairment in AD pathogenesis.

The emerging functions of oligodendrocytes in regulating neuronal network behaviour
Livia de Hoz and Mikael Simons, BioEssays, Volume 37, Issue 1, January 2015, in press.
DOI: 10.1002/bies.201400127

glia, myelin, networks, neurons, oligodendrocytes, plasticity

Beyond the role of myelin in speeding up nerve conduction, its function in the fine-tuning of neuronal networks is just emerging. This new concept of myelin plasticity implies that oligodendrocytes are able to sense neuronal activity and adapt myelination, resulting in a wider range of consequences than previously thought.

Experience and the ever-changing brain: What the transcriptome can reveal
Todd G. Rubin, Jason D. Gray and Bruce S. McEwen, BioEssays, Volume 36, Issue 11, November 2014, pages 1072-1081.
DOI: 10.1002/bies.201400095

epigenetics, gene expression, microarray, RNA-seq, stress

Transcriptional profiling techniques are revealing novel mechanisms underlying stress-induced neuroplasticity and yielding new insights into mood disorders. The image illustrates how the same stressor produces unique transcriptional profiles depending on the stress history of the mouse, highlighting how past experiences can alter cellular reactivity in certain dynamic brain regions.

Synthetic biology and therapeutic strategies for the degenerating brain
Carmen Agustín-Pavón and Mark Isalan, BioEssays, Volume 36, Issue 10, October 2014, pages 979-990.
DOI: 10.1002/bies.201400094

artificial cell systems, genome editing, neurodegeneration, synthetic proteins

Synthetic biology can help improve therapeutics for neurodegenerative diseases by providing novel synthetic molecules and proteins, intelligent gene circuits, genome editing tools, artificial cell systems, and vectors. These tools will allow more effective targeting of disease-related genes, controlled release of neuroprotective factors, and safer long-term therapies in human patients.

Cellular aging in depression: Permanent imprint or reversible process?
Josine E. Verhoeven, Dóra Révész, Owen M. Wolkowitz and Brenda W.J.H. Penninx, BioEssays, Volume 36, Issue 10, October 2014, pages 968-978.
DOI: 10.1002/bies.201400068

cellular aging, telomere length, telomerase, telomere homeostasis, depression, major depressive disorder, intervention studies

Should telomere shortening, an indicator of cellular aging, in depressed individuals be considered permanent damage or a reversible process? Some preliminary research suggests that telomere attrition may be decelerated or even reversed. This paper presents an overview of the current evidence, mechanistic pathways and targets for interventions.

Altered brain-gut axis in autism: Comorbidity or causative mechanisms?
Emeran A. Mayer, David Padua and Kirsten Tillisch, BioEssays, Volume 36, Issue 10, October 2014, pages 933-939.
DOI: 10.1002/bies.201400075

brain gut interactions, gut microbiome, intestinal permeability, neurodevelopment disorder

While proposed rodent models for autism spectrum disorder (ASD) are limited in modeling the complex human clinical phenotype(s) of ASD, they show both face and construct validity for several behavioral, gut physiological, brain signaling, and gut microbiome-related endophenotypes. Some of these models support a key role of alterations in the gut microbiome and its metabolism in the pathophysiology of ASD and common comorbidities.

Fez family transcription factors: Controlling neurogenesis and cell fate in the developing mammalian nervous system
Matthew J. Eckler and Bin Chen, BioEssays, Volume 36, Issue 8, August 2014, pages 788-797.
DOI: 10.1002/bies.201400039

cell fate, cerebral cortex, Fezf1, Fezf2, gene expression, neurogenesis, olfactory system

The zinc-finger transcription factors Fezf1 and Fezf2 are evolutionarily conserved from flies to humans. Within the developing mammalian nervous system they have unique and redundant functions during generation of the forebrain and olfactory system. These include coordination of neurogenic programs and the control of neuronal fate specification.