Cellular and Molecular Determinants of Stroke-Induced Changes in Subventricular Zone Cell Migration
Young CC, Brooks KJ, Buchan AM, Szele FG.
Department of Physiology, Anatomy and Genetics, University of... more
Young CC, Brooks KJ, Buchan AM, Szele FG.
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
A remarkable aspect of adult neurogenesis is that the tight regulation of subventricular zone (SVZ) neuroblast migration is altered after ischemic stroke and newborn neurons emigrate towards the injury. This phenomenon is an essential component of endogenous repair and also serves to illuminate normal mechanisms and rules that govern SVZ migration. Stroke causes inflammation that leads to cytokine and chemokine release, and SVZ neuroblasts that express their receptors are recruited. Metalloproteinases create pathways and new blood vessels provide a scaffold to facilitate neuroblast migration between the SVZ and the infarct. Most experiments have studied the peri-lesion parenchyma and relatively little is known about SVZ remodeling after stroke. Migration in the SVZ is tightly regulated by cellular interactions and molecular signaling; how are these altered after stroke to allow emigration? Do ependymal cells contribute to this process, given their reported neurogenic potential? How does stroke affect ependymal cell regulation of cerebrospinal fluid flow? Given the heterogeneity of SVZ progenitors, do all types of neuroblasts migrate out, or is this confined to specific subtypes of cells? We discuss these and other questions in our review and propose experiments to address them.
SILENCED MAJORITY
Written in 2005-06 . Edited four times.
It is an essay reflectinhg on how Indians in Guyana, even being a majority are silenced both by their own government... more It is an essay reflectinhg on how Indians in Guyana, even being a majority are silenced both by their own government and larger society
From Microscopic to Macroscopic Descriptions of Cell Migration on Growing Domains
R.E. Baker, C.A. Yates and R. Erban (2009). "From Microscopic to Macroscopic Descriptions of Cell Migration on Growing Domains ". Bulletin of Mathematical Biology 72(3) 719-762.
Cell migration and growth are essential components of the development of multicellular organisms. The role of various... more
Cell migration and growth are essential components of the development of multicellular organisms. The role of various cues in directing cell migration is widespread, in particular, the role of signals in the environment in the control of cell motility and directional guidance. In many cases, especially in developmental biology, growth of the domain also plays a large role in the distribution of cells and, in some cases, cell or signal distribution may actually drive domain growth. There is an almost ubiquitous use of partial differential equations (PDEs) for modelling the time evolution of cellular density and environmental cues. In the last 20 years, a lot of attention has been devoted to connecting macroscopic PDEs with more detailed microscopic models of cellular motility, including
models of directional sensing and signal transduction pathways. However, domain growth is largely omitted in the literature. In this paper, individual-based models describing cell
movement and domain growth are studied, and correspondence with a macroscopic-level PDE describing the evolution of cell density is demonstrated. The individual-based models
are formulated in terms of random walkers on a lattice. Domain growth provides an extra mathematical challenge by making the lattice size variable over time. A reaction-diffusion master equation formalism is generalised to the case of growing lattices and used in the derivation of the macroscopic PDEs.
Tes, a specific Mena interacting partner, breaks the rules for EVH1 binding.
by David Briggs
Joint First Author, I did strucutral work and the calorimetry, Batiste did the Cell Culture work and microscopy. IMHO, my best work to date. (Even though Nature & Science rejected it!)
The intracellular targeting of Ena/VASP family members is achieved via the interaction of their EVH1 domain with FPPPP... more The intracellular targeting of Ena/VASP family members is achieved via the interaction of their EVH1 domain with FPPPP sequence motifs found in a variety of cytoskeletal proteins, including lamellipodin, vinculin, and zyxin. Here we show that the LIM3 domain of Tes, which lacks the FPPPP motif, binds to the EVH1 domain of Mena, but not to those of VASP or Evl. The structure of the LIM3:EVH1 complex reveals that Tes occludes the FPPPP-binding site and competes with FPPPP-containing proteins for EVH1 binding. Structure-based gain-of-function experiments define the molecular basis for the specificity of the Tes-Mena interaction. Consistent with in vitro observations, the LIM3 domain displaces Mena, but not VASP, from the leading edge and focal adhesions. It also regulates cell migration through a Mena-dependent mechanism. Our observations identify Tes as an atypical EVH1 binding partner and a regulator specific to a single Ena/VASP family member.
