Lewis-Sigler Theory Fellow Lewis-Sigler Institute for Integrative Genomics Department of Physics Princeton University
261 Carl-Icahn Laboratory Princeton NJ, 08544
Email: kaschube[a]princeton edu Phone: +1 (609) 258-1937
Biological physics of collective behavior of cells
Many interesting phenomena arise when passing from the single-cell to the multi-cell level. Striking examples are networks of neurons in sensory cortical areas that are capable of 'processing' sensory input, or the precise morphgenetic changes that take place in a developing embryo. These complex tasks require the orchestrated interplay of a large collection of individual cells. What mechanisms organize cells to such a highly elaborate level?
Whereas processes in individual cells are relatively well studied, the mechanisms by which these processes are coordinated among multiple cells are much less understood. In my lab we explore the principles governing the formation of collective processes that involve many cells and underlie such remarkable tasks as vision or morphogenesis. For instance, in the primary visual cortex we study the role of cortical interactions in learning to perceive motion in viusal stimuli. In fruit fly embryos we ask how individual cells coordinate their shape changes to robustlyly realize the formation of the ventral furrow during early gastrulation.
Some specific projects:
Apical constriction and its coordination across cells in ventral furrow formation in fruit flies
With Adam Martin and Eric Wieschaus (Department of Molecular Biology)
How
do individual cells dynamically coordinate their behavior to realize
morphogenetic changes on the tissue level? By combining quantitative
analysis of live-cell imaging data with physical models we seek to
reveal the nature of cell-cell interactions that play a role in ventral
furrow formation during early gastrulation in fruit flies. In a recent
study (A. Martin, M. Kaschube, E. Wieschaus, Nature, in press) we
revealed a novel ‘ratchet’ mechanism for apical constriction in ventral
furrow cells. We showed that apical constriction is pulsed, with
phases of constriction interrupted by pauses in which the cell size is
maintained. Actin-myosin network contractions on the apical
cortex drive constriction. Our results contrast with the
conventional model in which an actin-myosin purse-string causes
continuous constriction. We found that the transcription factors
twist and snail differentially regulate the separate phases of the
contraction cycle, demonstrating how the activities of these genes are
coordinated to produce shape changes in individual cells. Currently, we
study how these processes are coordinated among different cells.
The role of self-organization in development of direction selectivity in the visual cortex.
In collaboration with Len White, Steve van Hooser and David Fitzpatrick (Duke University)
Experience
with moving visual stimuli drives the early development of direction
selectivity in the visual cortex (Ye et al., Nature, 2008).
However, alsothe state of the cortical network appears to have a strong
affect on whether a given neuron becomes selective for one stimulus
direction or the other. If most of its surrounding neurons prefer a
given direction, a cell is more likely to become selective for the same
direction, even if exposed predominantly to stimuli of the opposite
direction (Van Hooser et al., SfN, 2008). We combine mathematical
modelling and quantitative analysis of two-photon calcium imaging data
of a collection of visual cortical cells to dissect the interplay
between the external training stimulus and neuronal interactions that
shapes a neural circuitry capable of robustly processing motion
components in natural stimuli. In one recent study we focused on the
response properties of individual direction selective simple cells and
revealed the important role of inhibitory inputs in rendering these
neurons selective (Liu et al. , SfN, 2008). In particular, when
inhibitory inputs are tuned in the same direction as excitatory inputs
(as observed by Priebe and Ferster, Neuron, 2005) cells respond highly
selective, even for stimuli presented only over a short period
(~100ms).
Reorganization of neuronal circuits in growing visual cortex
Together
with Wolfgang Keil, a visiting grad student at Princeton
University.
The dynamics of reorganization of large
cortical circuits is rooted in plasticity of individual synapses, but
rules governing the collective behavior of large networks of neurons
are only poorly understood. The postnatal brain growth partly evoked by
extensive formation of new synaptic connections may expose cortical
areas to a 'natural perturbation' sufficiently strong to observe
signatures of large scale reorganization. In a recent study (Keil et
al, SfN, 2008) we observed by quantifying large sets of imaging data
from juvenile cat visual cortex a novel mode of reorganization of
domains that prefer inputs from one eye or the other. Our
theoretical analysis shows that this mode can be explained
quantitatively by the so called Zigzag instability, a dynamical
reorganization, well-known in the field of pattern formation in
physics, by which 2D isotropic Turing patterns respond to an increase
in their typical spatial scale with a zigzag-like bending of domains.
We point out that this instability has in fact been predicted, albeit
implicitly, by most models of visual cortical development that have
been proposed so far. These results indicate that during normal
postnatal development cortical networks can undergo large scale
reorganizations during which cortical neurons shift their response
properties in a spatially coordinated and activity dependent fashion.
Universality in the evolution of orientation columns in the visual cortex
With Fred Wolf (MPIDS Goettingen), Len White (Duke), Siegrid Loewel (Jena) and David Coppola (Randolph Macon)
Since
the basal radiation of placental mammals 65 million years ago, genetic
changes have accumulated that underlie marked phenotypic differences
expressed across mammalian clades. In this project, we analyzed
systems of orientation columns in the visual cortex of long-separated
species that occupy widely different ecological niches and demonstrate
that there are quantitative rules that govern the design of neuronal
networks from which evolutionary modification can hardly deviate. Thus,
in primate (galago), carnivora (ferret) and scandentia (tree shrew) the
layout of orientation columns precisely follows a single universal
design. We characterize the universal design by a series of
invariant quantitative laws that govern the layout of orientation
columns in the visual cortex. Furthermore, we show that the robust
formation and evolutionary preservation of the universal design can be
explained as a consequence of cortical network self-organization. This
is achieved through a mathematical analysis of models for the dynamical
self-organization of orientation columns. We demonstrate that all
features of the universal design robustly emerge, when neuronal
self-organization is dominated by long-ranging interactions. Thus the
universal design will emerge in any species that ontogenetically builds
its contour processing networks by such a process. This fact can
explain the evolutionary emergence and preservation of the universal
design without reference to selective pressures on the visual system
and without the existence of a common ancestor exhibiting the universal
design.
Selected publications
Pulsed
contractions of an actin-myosin network drive apical constriction. A.C.
Martin, M. Kaschube, E.F. Wieschaus, Nature, 2008, doi:
10.1038/nature07522 PubMed
Self-organization
and the selection of pinwheel density in visual cortical development.
M. Kaschube, M. Schnabel, and F. Wolf, New Journal of Physics, 10,
015009, 2008. Journal
Random
Waves in the Brain: Symmetries and Defect Generation in the Visual
Cortex. M. Schnabel, M. Kaschube, S. Loewel and F. Wolf,
Europhysics Journal Special Topics 145, 137-157, 2007. Journal
The
pattern of ocular dominance columns in cat primary visual cortex:
Intra- and interindividual variability of column spacing and its
dependence on genetic background. M. Kaschube, F. Wolf, M. Puhlmann, S.
Rathjen, K.-F. Schmidt, T. Geisel, and S. Loewel. European Journal of
Neuroscience, 18:3251-3266, 2003. PubMed
Genetic
influence on quantitative features of neocortical architecture. M.
Kaschube, F. Wolf, T. Geisel, and S. Loewel. Journal of
Neuroscience, 22(16):7206-7217, 2002. PubMed
On the archive
Pinwheel stability, pattern selection and the geometry of visual space. M. Schnabel, M. Kaschube, F. Wolf, arXiv:0801.3832 arXiv
Inter-areal
coordination of columnar architectures during visual cortical
development. M. Kaschube, M. Schnabel, S. Löwel, F. Wolf,
arXiv:0801.4164 arXiv