A new model for freedom of movement using connectomic analysis.

The problem of whether we can execute free acts or not is central in philosophical thought, and it has been studied by numerous scholars throughout the centuries. Recently, neurosciences have entered this topic contributing new data and insights into the neuroanatomical basis of cognitive processes. With the advent of connectomics, a more refined landscape of brain connectivity can be analysed at an unprecedented level of detail. Here, we identify the connectivity network involved in the movement process from a connectomics point of view, from its motivation through its execution until the sense of agency develops. We constructed a "volitional network" using data derived from the Brainnetome Atlas database considering areas involved in volitional processes as known in the literature. We divided this process into eight processes and used Graph Theory to measure several structural properties of the network. Our results show that the volitional network is small-world and that it contains four communities. Nodes of the right hemisphere are contained in three of these communities whereas nodes of the left hemisphere only in two. Centrality measures indicate the nucleus accumbens is one of the most connected nodes in the network. Extensive connectivity is observed in all processes except in Decision (to move) and modulation of Agency, which might correlate with a mismatch mechanism for perception of Agency.

A Notch-regulated proliferative stem cell zone in the developing spinal cord is an ancestral vertebrate trait.

Vertebrates have evolved the most sophisticated nervous systems we know. These differ from the nervous systems of invertebrates in several ways, including the evolution of new cell types, and the emergence and elaboration of patterning mechanisms to organise cells in time and space. Vertebrates also generally have many more cells in their central nervous systems than invertebrates, and an increase in neural cell number may have contributed to the sophisticated anatomy of the brain and spinal cord. Here, we study how increased cell number evolved in the vertebrate central nervous system, investigating the regulation of cell proliferation in the lamprey spinal cord. Markers of proliferation show that a ventricular progenitor zone is found throughout the lamprey spinal cord. We show that inhibition of Notch signalling disrupts the maintenance of this zone. When Notch is blocked, progenitor cells differentiate precociously, the proliferative ventricular zone is lost and differentiation markers become expressed throughout the spinal cord. Comparison with other chordates suggests that the emergence of a persistent Notch-regulated proliferative progenitor zone was a crucial step for the evolution of vertebrate spinal cord complexity.

The structure, splicing, synteny and expression of lamprey COE genes and the evolution of the COE gene family in chordates.

COE genes encode transcription factors that have been found in all metazoans examined to date. They possess a distinctive domain structure that includes a DNA-binding domain (DBD), an IPT/TIG domain and a helix-loop-helix (HLH) domain. An intriguing feature of the COE HLH domain is that in jawed vertebrates it is composed of three helices, compared to two in invertebrates. We report the isolation and expression of two COE genes from the brook lamprey Lampetra planeri and compare these to COE genes from the lampreys Lethenteron japonicum and Petromyzon marinus. Molecular phylogenetic analyses do not resolve the relationship of lamprey COE genes to jawed vertebrate paralogues, though synteny mapping shows that they all derive from duplication of a common ancestral genomic region. All lamprey genes encode conserved DBD, IPT/TIG and HLH domains; however, the HLH domain of lamprey COE-A genes encodes only two helices while COE-B encodes three helices. We also identified COE-B splice variants encoding either two or three helices in the HLH domain, along with other COE-A and COE-B splice variants affecting the DBD and C-terminal transactivation regions. In situ hybridisation revealed expression in the lamprey nervous system including the brain, spinal cord and cranial sensory ganglia. We also detected expression of both genes in mesenchyme in the pharyngeal arches and underlying the notochord. This allows us to establish the primitive vertebrate expression pattern for COE genes and compare this to that of invertebrate chordates and other animals to develop a model for COE gene evolution in chordates.

Characterization of two neurogenin genes from the brook lamprey lampetra planeri and their expression in the lamprey nervous system.

CONCLUSIONS: Neurogenins are required for the specification of neuronal precursors and regulate the expression of basic Helix-Loop-Helix genes involved in neuronal differentiation. Jawed vertebrates possess three Neurogenin paralogy groups and their combined expression covers the entire nervous system, apart from the autonomic nervous system. RESULTS: Here we report the isolation of two Neurogenin genes, LpNgnA and LpNgnB, from the lamprey Lampetra planeri. Phylogenetic analyses show both genes have orthologues in other lamprey species and in a hagfish. Neither gene shows evidence of orthology to specific jawed vertebrate Neurogenin paralogues. LpNgnA is expressed in the ventricular zone of regions of the brain and spinal cord, with expression in the brain demarcating brain sub-compartments including the pallium, tegmentum, tectum, and dorsal thalamus. In the peripheral nervous system, LpNgnA is expressed in cranial sensory placodes and their derivatives, and in the dorsal root ganglia. LpNgnB is expressed transiently in placodal head ectoderm and throughout the central nervous system in early development, and in a small population cells that form part of the macula. CONCLUSIONS: Combined, LpNgnA and LpNgnB were detected in most cell populations marked by Neurogenin gene expression in jawed vertebrates, with the exception of the cerebellum, retina and the non-neural expression sites. Developmental Dynamics 244:1096-1108, 2015. © 2015 Wiley Periodicals, Inc.

Retinoic acid signaling in spinal cord development.

Retinoic acid (RA) is an important signaling molecule mediating intercellular communication through vertebrate development. Here, we present and discuss recent information on the roles of the RA signaling pathway in spinal cord development. RA is an important player in the patterning and definition of the spinal cord territory from very early stages of development, even before the appearance of the neural plate and further serves a role in the patterning of the spinal cord both along the dorsoventral and anteroposterior axes, particularly in the promotion of neuronal differentiation. It is thus required to establish a variety of neuronal cell types at specific positions of the spinal cord. The main goal of this review is to gather information from vertebrate models, including fish, frogs, chicken and mice, and to put this information in a comparative context in an effort to visualize how the RA pathway was incorporated into the evolving vertebrate spinal cord and to identify mechanisms that are both common and different in the various vertebrate models. In doing so, we try to reconstruct how spinal cord development has been regulated by the RA signaling cascade through vertebrate diversification, highlighting areas which require further studies to obtain a better understanding of the evolutionary events that shaped this structure in the vertebrate lineage.