Organ formation requires coordinating signals to time proliferation, specify cell fates, and shape tissue. Tracing these events the that drive them remains a challenge, as intermediate states across many critical transitions are unresolvable over real space. Here, we designed unique computational approach decompose non-linear differentiation process into biological meaningful components resolve...

Dorsoventral pattern of Drosophila embryo is specified by the nuclear localization gradient of the transcription factor Dorsal. Genetic and genomic studies of this morphogen gradient provided important insights into spatial control of gene expression in development. Recent live imaging experiments revealed hitherto unappreciated dynamics of the Dorsal gradient and posed new questions about the ...

GENE EXPRESSION IS A NOISY STOCHASTIC PROCESS, SINCE IT INVOLVES AT ITS CORE INTERACTIONS BETWEEN SINGLE MOLECULES: a polymerase and a binding site. However, many biological processes directly dependent upon gene expression are reliable. Prominent among them is morphogenesis: how are body parts so consistently generated and proportioned? In the early embryo, gradients of certain proteins called...

Quantitative information about the distribution of morphogens is crucial for understanding their effects on cell-fate determination, yet it is difficult to obtain through direct measurements. We have developed a parameter estimation approach for quantifying the spatial distribution of Gurken, a TGFalpha-like EGFR ligand that acts as a morphogen in Drosophila oogenesis. Modeling of Gurken/EGFR s...

During embryonic development, differentiating cells respond via gene expression to positional cues from morphogen gradients. While gene expression is often highly erratic, embryonic development is precise. We show by theory and simulations that diffusion of the expressed protein can enhance the precision of its expression domain. While diffusion lessens the sharpness of the expression boundary,...

During embryonic development, differentiating cells respond via gene expression to positional cues from morphogen gradients. While gene expression is often highly erratic, embryonic development is precise. We show by theory and simulations that diffusion of the expressed protein can enhance the precision of its expression domain. While diffusion lessens the sharpness of the expression boundary,...

A crucial issue in studies of morphogen gradients relates to their range: the distance over which they can act as direct regulators of cell signaling, gene expression and cell differentiation. To address this, we present a straightforward statistical framework that can be used in multiple developmental systems. We illustrate the developed approach by providing a point estimate and confidence in...

1 Chapter 1: Introduction 2 1.1. Overview 2 1.2. Hypothesis and Specific Aims 7 Chapter 2: Background 9 2.1. Importance of Gradients in Tissue Engineering 9 2.1.1. Morphogen gradients 9 2.1.2. Bone/cartilage interface 14 2.1.3. Bone /ligament and bone/tendon interfaces 18 2.2. RNA Interference and siRNA Delivery 22 2.2.1. Overview of RNA interference 22 2.2.2. Applications of siRNA in tissue en...

The leftward flow in extraembryonic fluid is critical for the initial determination of the left-right axis of mouse embryos. It is unclear if this is a conserved mechanism among other vertebrates and how the directionality of the flow arises from the motion of cilia. In this paper, we show that rabbit and medakafish embryos also exhibit a leftward fluid flow in their ventral nodes. In all cases...