A study of the generation of diversity in the central nervous system

Developmental biology is concerned with understanding the mechanisms that govern the generation of a whole organism starting from one single cell. In the central nervous system (CNS) the development of different classes of neurons and glial cells involves both extrinsic signals and intrinsic cues that together govern the specification of different cell fates dependent on position within the CNS and the time of generation. Different vertebrate species share many aspects of early development as well as the underlying mechanisms governing the progress of development. Therefore, a plausible assumption is that functional regions in the genome are also conserved between species. In Paper I, we have used a comparative genomics approach to identify Highly Conserved Non‐coding Regions (HCNRs) between the human, mouse and pufferfish genomes. We find HCNRs to be statistically over represented in the proximity of transcription factors associated with spatial patterning in the developing neural tube. We show that HCNRs associated with patterning genes show an overrepresentation of binding sites for three transcription factors (Sox, Pou and Homedomain genes (SPHD)). By combining bioinformatics and large-scale expression analysis, we show that SPHD enriched HCNRs are strong predictors of CNS expression during development (83% vs. 36% of random control genes). This suggested to us that SPHD+ HCNRs may act as CNS enhancers. Further, we isolate a putative HCNR enhancer region and show that it acts as an enhancer both in vivo and in vitro. Based on our findings, we propose a model where Sox and Pou proteins act as common activators of CNS expressed genes, while homeodomain proteins, which have been previously shown to act as repressors, act to restrict expression spatially. While a large number of studies have provided insight into the spatial patterning mechanisms directing the generation of distinct cell types at different positions, little is known about the temporal mechanisms underlying the specification of different cell types from a common pool of progenitors in the CNS. In Paper II, we have addressed the question of how a seemingly homogenous population of progenitor cells in the caudal hindbrain can give rise to distinct subtypes of vagal visceral motoneurons (vMNs). We show that based on molecular marker expression we can distinguish between at least three subtypes of vMNs at early developmental time points and that each subtypes corresponds to a distinct projections pattern in the periphery. We show that these subtypes are generated sequentially and that the decision to become a specific subtype is independent of contacts with peripheral targets and cell‐cell mediated interactions. Further, the homeodomain transcription factor Nkx6.1 and the orphan nuclear receptor Nurr1 are required for the specification of early born subtypes and the maturation of late born subtypes, respectively. In Paper III we were concerned with the origins of oligodendrocytes in the developing spinal cord and hindbrain. Oligodendrocytes have been shown to be generated from a ventrally located domain in the spinal cord and while this ventral origin has been widely accepted, the existence of other origins remained subject to debate. We show, based on in vitro cultures as well as mutant analysis, that dorsal domains in the spinal cord can give rise to oligodendrocyte precursors and that these precursors have the capacity to develop to bona‐fide mature oligodendrocytes based on expression of mature markers. Further we show that, at least at prenatal stages, ventrally and dorsally generated oligodendrocytes exhibit differences in expression profiles, suggesting potential differences between these populations. Additionally, our data suggests that the decrease in BMP signaling, a known inhibitor of oligodendrogenesis, in the dorsal spinal cord over time, due to the increase in the size of the neural tube, may influence the time of induction of the dorsally generated oligodendrocyte precursors in spinal cord. Also, our data from the spinal cord and the hindbrain, show that ventral oligodendrogenesis at different anteroposterior levels is governed by different genetic programs

Screening Masses in SU(2) Pure Gauge Theory

We perform a systematic scaling study of screening masses in pure gauge SU(2) theory at temperatures above the phase transition temperature. The major finite volume effect is seen to be spatial deconfinement. We extract the screening masses in the infinite volume and zero lattice spacing limit. We find that these physical results can be deduced from runs on rather coarse lattices. Dimensional reduction is clearly seen in the spectrum.Comment: 14 pages, 3 figures. Minor change in Figs. 2 & 3 and discussion. Main results unchange

Polyakov Loop Dynamics in the Center Symmetric Phase

A study of the center symmetric phase of SU(2) Yang Mills theory is presented. Realization of the center symmetry is shown to result from non-perturbative gauge fixing. Dictated by the center symmetry, this phase exhibits already at the perturbative level confinement like properties. The analysis is performed by investigating the dynamics of the Polyakov loops. The ultralocality of these degrees of freedom implies significant changes in the vacuum structure of the theory. General properties of the confined phase and of the transition to the deconfined phase are discussed. Perturbation theory built upon the vacuum of ultralocal Polyakov loops is presented and used to calculate, via the Polyakov loop correlator, the static quark-antiquark potential.Comment: 45 pages, LaTeX, 8 figure

Constructing the fermion-boson vertex in QED3

We derive perturbative constraints on the transverse part of the fermion-boson vertex in massive QED3 through its one loop evaluation in an arbitrary covariant gauge. Written in a particular form, these constraints naturally lead us to the first non-perturbative construction of the vertex, which is in complete agreement with its one loop expansion in all momentum regimes. Without affecting its one-loop perturbative properties, we also construct an effective vertex in such a way that the unknown functions defining it have no dependence on the angle between the incoming and outgoing fermion momenta. Such a vertex should be useful for the numerical study of dynamical chiral symmetry breaking, leading to more reliable results.Comment: 13 pages, 2 figure

The Standard Model of Leptons as a Purely Vectorial Theory

We propose a way to reconcile the Standard Model of leptons with a purely vectorial theory. The observed neutrino is predicted to be massless. The unobservability of its partner and the $V-A$ structure of the weak currents are given the same origin.Comment: 10 pages. Latex, 8 postscript figures included. We have corrected 2 (cancelling) sign misprints, and made explicit that we also recover the usual couplings of the U(1) gauge field B. The conclusions are unchanged. PAR-LPTHE 93/1

Debye mass from domainwalls and dimensionally reduced phase diagram

To measure the Debye mass in dimensionally reduced QCD for $N_c\le 3$ we replace in the correlator of two Polyakov loops one of the loops by a wall triggered by a dimensionally reduced twist. The phase diagram for $N_c=3$ has R-parity broken in part of the Higgs phase.Comment: LATTICE98(hightemp

The Two-Loop Finite-Temperature Effective Potential of the MSSM and Baryogenesis

We construct an effective three dimensional theory for the MSSM at high temperatures in the limit of large-$m_{A}$. We analyse the two-loop effective potential of the 3D theory for the case of a light right handed stop to determine the precise region in the $m_{h}$-$m_{\tilde{t}_{R}}$ plane for which the sphaleron constraint for preservation of the baryon asymmetry is satisfied. We also compare with results previously obtained usind 3D and 4D calculations of the effective potential. A two-stage phase transition still persists for a small range of values of $m_{\tilde{t}_{R}}$. The allowed region requires a value of m_{\tilde{t}_{R}} \lsi m_{t} and m_{h} \lsi 100 (110) GeV for $m_{Q} = 300$ GeV (1 TeV).Comment: 40 pages, 6 Postcsript figures, uses eps

Anisotropic evolution of 5D Friedmann-Robertson-Walker spacetime

We examine the time evolution of the five-dimensional Einstein field equations subjected to a flat, anisotropic Robertson-Walker metric, where the 3D and higher-dimensional scale factors are allowed to dynamically evolve at different rates. By adopting equations of state relating the 3D and higher-dimensional pressures to the density, we obtain an exact expression relating the higher-dimensional scale factor to a function of the 3D scale factor. This relation allows us to write the Friedmann-Robertson-Walker field equations exclusively in terms of the 3D scale factor, thus yielding a set of 4D effective Friedmann-Robertson-Walker field equations. We examine the effective field equations in the general case and obtain an exact expression relating a function of the 3D scale factor to the time. This expression involves a hypergeometric function and cannot, in general, be inverted to yield an analytical expression for the 3D scale factor as a function of time. When the hypergeometric function is expanded for small and large arguments, we obtain a generalized treatment of the dynamical compactification scenario of Mohammedi [Phys.Rev.D 65, 104018 (2002)] and the 5D vacuum solution of Chodos and Detweiler [Phys.Rev.D 21, 2167 (1980)], respectively. By expanding the hypergeometric function near a branch point, we obtain the perturbative solution for the 3D scale factor in the small time regime. This solution exhibits accelerated expansion, which, remarkably, is independent of the value of the 4D equation of state parameter w. This early-time epoch of accelerated expansion arises naturally out of the anisotropic evolution of 5D spacetime when the pressure in the extra dimension is negative and offers a possible alternative to scalar field inflationary theory.Comment: 20 pages, 4 figures, paper format streamlined with main results emphasized and details pushed to appendixes, current version matches that of published versio

Singular behaviour of the electromagnetic field

The singularities of the electromagnetic field are derived to include all the point-like multipoles representing an electric charge and current distribution. Firstly derived in the static case, the result is generalized to the dynamic one. We establish a simple procedure for passing from the first, to the second case.Comment: Latex, 21.pages, no figure