Charles D. Little, PhD

Anatomy and Cell Biology

Ph.D.: 1977, University of Pittsburgh, Pittsburgh
Postdoctoral: 1979, Harvard Medical School, Boston
Postdoctoral: 1981, University of California, San Diego
Postdoctoral: 1981, University of California, San Diego

As we begin the new century biologists are rediscovering the elegant embryology that flourished at the beginning of the last century. Modern developmental biologists are beginning to place earlier embryological studies on a firm cellular and molecular basis. Sophisticated probes for specific molecular mechanisms have stimulated a renaissance in the use of the light microscope. Fluorescent markers, digital image processing and intravital labeling methods have had a major impact on understanding vertebrate morphogenesis. Our scientific goal is to understand early morphogenesis, particularly vessel formation and vertebral axis formation.

To accomplish this goal we have joined with physicists and mathematicians to develop software and instrumentation to enable time lapse microscopy of morphogenic processes in intact embryos, in this case quail and chicken. We are blending traditional microscopic approaches with state-of-the-art dynamic computational biology. This new digital technology allows measurement and quantification of behaviors, both of individual cells and the whole biological ensemble.

We culture early avian embryos into which we inject probes and reagents designed to perturb specific extracellular molecular events. For example, reagents hypothesized to regulate endothelial tube or somite formation. Integrins, matrix metalloproteinases, ECM glycoproteins, and vascular growth factors are all molecular targets for experimental perturbation. To assay the effects of experimental manipulation we have devised the means to record differential interference contrast and fluorescence optical images in a time-lapse mode. Data are stored to computer hard drives, processed using software of our own design and rendered as QuickTime move clips. Our computational algorithms allow a connection to be made between the large-scale, macroscopic behavior of a system and the microscopic interactions of its constituents. Using the concepts and methods of statistical physics, a predictive insight into the cellular mechanisms leading to collective biological behavior can be reached.

We hope to understand complex biological processes involving the simultaneous interaction of multicellular assemblies during embryogenesis. The proper quantification of dynamic cell/tissue behavior can illuminate otherwise undecipherable biological principles. While it may be that molecular mechanisms trigger developmental change, it is collective cell behavior that is the hallmark of morphogenesis.

Recent Publications

  1. Rupp, P.A., Czirók, A. and Little, C.D. anb3 Integrin dependent endothelial cell dynamics, in vivo. Development 131, 2887-2897, 2004.
  2. Zamir, E.A., Czirók, A., Cui, C., Little, C.D., and Rongish, B.J. Mesodermal Cell Displacements during Avian Gastrulation are due to Individual Cell-Autonomous and Convective Tissue Movements. Proc. Nat. Acad. Sci, USA, 103:52, 19806-19811, 2006.
  3. Czirók, A., Zamir, E.A., Filla, M.B., Little, C.D., and Rongish, B.J. Extracellular matrix macro-assembly dynamics in early vertebrate embryos. In: Current Topics in Developmental Biology, Vol.3; pp237-258, 2006.
  4. Czirók, A., Zamir, E. A., Szabo, A. and Little, C.D.; Multicellular sprouting during vasculogenesis, In: Current Topics Developmental Biology, Multiscale Modeling of Developmental Systems, 81:269-289, 2007.
  5. Perryn, E.D., Czirók, A. and Little, C.D. Vascular sprout formation entails tissue deformations and VE-cadherin dependent cell-autonomous motility, Dev. Biol. 313:545 555, 2008.
  6. Zamir, E.A., Rongish, B.J and Little, C.D., The ECM moves during primitive streak formation—computation of ECM versus cellular motion. PLoS, Biology, 2008 October; 6(10): 2163-2171, 2008. doi:10.1371/journal.pbio.0060247.
  7. Rupp, P.A., Visconti, R.P., Czirok, A., Cheresh, D.A., and Little, C.D. Matrix Metalloproteinase 2-Integrin avb3 Binding Is Required for Mesenchymal Cell Invasive Activity but Not Epithelial Locomotion: A Computational Time-Lapse Study. Mol. Biol. Cell, 19:5529 –5540, 2008: doi10.1091/mbc.E07-05-0480.
  8. Cheng, C., Little, C.D., Rongish, B.J. Rotation of organizer tissue confers left-right asymmetry, Anat. Rec. 2009 292(4):557-561; PMID: 19301278.

Other Support

2R01HL068855-07A1 (Little, Charles D.)
06/18/2008 - 05/31/2012, 3 calendar
NIH, $284,727
Computational Biology of Vascular Cell Behavior
Major Goals The goals of this work are: 1) To establish a dynamic conceptual framework of how primary vascular patterns emerge in warm-blooded animals; 2) To prepare lineage-fate maps of angioblasts and their progeny — and thereby define the primary spatiotemporal pattern of vascular-specific gene expression; 3) To determine the function of key signaling molecules implicated in vascular cell-autonomous motility and differentiation; and 4) To develop biologically-grounded mathematical models and computer simulations of vasculogenesis in amniotes.

4630802 (Glazier, James. I.)
9/01/2005– 8/31/2008, 0.48 calendar
Biocomplexity Institute, Indiana $48,951 (sub-project only)
(NIH grant # R01GM76692)
Multiscale Studies of Segmentation in Vertebrate Embryos
Sub-Project Title: Computational Imaging of Segmentation in Vertebrate Embryos Dr. Little’s group will provide empirical data for the Cellular Potts model being constructed by the Glazier group. In addition the Little Lab will serve as consultants for experimental embryology.
Role: Co-Investigator
Award letter 11/14/2008 (Little, C)
01/01/2009 - 12/31/2011, 0.6 calendar

Mathers Charitable Foundation
$162,315 per year
Deciphering the biomechanical morphogenetic code
The major goals of this project are to determine if inherent tension fields govern the patterning of cells and tissues during caudal axis formation, and to perform biomechanical perturbations of axial tissues to observe and quantify resulting phenotypes in the caudal embryo.

Last modified: Apr 15, 2014

Charles D. Little, PhD


Charles D. Little, PhD