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Publications

A Geometric Model of Stripe Refinement

Cornell Affiliated Author(s)
Author
E.D. Siggia
Abstract

Organizing data about patterning and morphogenesis into a coherent framework remains a challenge in developmental biology. Reporting in Science, Corson et al. (2017) apply innovative analysis to an old problem of bristle patterns in Drosophila, reducing the nonlinear interactions among tens of cells to a succinct model with quantitative predictions. © 2017 Elsevier Inc.

Journal
Developmental Cell
Date Published
Funding Source
1502151
Research Area

Long-Term High-Resolution Imaging of Developing C. elegans Larvae with Microfluidics

Cornell Affiliated Author(s)
Author
W. Keil
L.M. Kutscher
S. Shaham
E.D. Siggia
Abstract

Long-term studies of Caenorhabditis elegans larval development traditionally require tedious manual observations because larvae must move to develop, and existing immobilization techniques either perturb development or are unsuited for young larvae. Here, we present a simple microfluidic device to simultaneously follow development of ten C. elegans larvae at high spatiotemporal resolution from hatching to adulthood (∼3 days).

Journal
Developmental Cell
Date Published
Funding Source
ECCS-1542081
HD078703
NS064273
NS081490
PHY 1502151
LT000250/2013-C
P40 OD010440
R01HD078703
GM066699
Research Area

A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization

Cornell Affiliated Author(s)
Author
F. Etoc
J. Metzger
A. Ruzo
C. Kirst
A. Yoney
M.Z. Ozair
A.H. Brivanlou
E.D. Siggia
Abstract

The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo, we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These gastruloids recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula.

Journal
Developmental Cell
Date Published
Funding Source
PHY-1502151
R01HD080699
-132526
2014-001
Research Area

Self-organization of human embryonic stem cells on micropatterns

Cornell Affiliated Author(s)
Author
A. Deglincerti
F. Etoc
M.C. Guerra
I. Martyn
J. Metzger
A. Ruzo
M. Simunovic
A. Yoney
A.H. Brivanlou
E. Siggia
A. Warmflash
Abstract

Fate allocation in the gastrulating embryo is spatially organized as cells differentiate into specialized cell types depending on their positions with respect to the body axes. There is a need for in vitro protocols that allow the study of spatial organization associated with this developmental transition. Although embryoid bodies and organoids can exhibit some spatial organization of differentiated cells, methods that generate embryoid bodies or organoids do not yield consistent and fully reproducible results.

Journal
Nature Protocols
Date Published
Funding Source
R01HD080699
Research Area

Small-scale anisotropy in turbulent boundary layers

Cornell Affiliated Author(s)
Author
A. Pumir
H. Xu
E.D. Siggia
Abstract

In a channel flow, the velocity fluctuations are inhomogeneous and anisotropic. Yet, the small-scale properties of the flow are expected to behave in an isotropic manner in the very-large-Reynolds-number limit. We consider the statistical properties of small-scale velocity fluctuations in a turbulent channel flow at moderately high Reynolds number , using the Johns Hopkins University Turbulence Database.

Journal
Journal of Fluid Mechanics
Date Published
Research Area

Predicting Ancestral Segmentation Phenotypes from Drosophila to Anopheles Using In Silico Evolution

Cornell Affiliated Author(s)
Author
J.B. Rothschild
P. Tsimiklis
E.D. Siggia
P. François
Abstract

Molecular evolution is an established technique for inferring gene homology but regulatory DNA turns over so rapidly that inference of ancestral networks is often impossible. In silico evolution is used to compute the most parsimonious path in regulatory space for anterior-posterior patterning linking two Dipterian species. The expression pattern of gap genes has evolved between Drosophila (fly) and Anopheles (mosquito), yet one of their targets, eve, has remained invariant.

Journal
PLoS Genetics
Date Published
Funding Source
1502151
Research Area

Self-organization of the in vitro attached human embryo

Cornell Affiliated Author(s)
Author
A. Deglincerti
G.F. Croft
L.N. Pietila
M. Zernicka-Goetz
E.D. Siggia
A.H. Brivanlou
Abstract

Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system to study the post-implantation development of the human embryo.

Journal
Nature
Date Published
Research Area

Temperature compensation and temperature sensation in the circadian clock

Cornell Affiliated Author(s)
Author
P.B. Kidd
M.W. Young
E.D. Siggia
Abstract

All known circadian clocks have an endogenous period that is remarkably insensitive to temperature, a property known as temperature compensation, while at the same time being readily entrained by a diurnal temperature oscillation. Although temperature compensation and entrainment are defining features of circadian clocks, their mechanisms remain poorly understood.

Journal
Proceedings of the National Academy of Sciences of the United States of America
Date Published
Funding Source
PHY-0954398
PHY-1502151
R01GM054339
Research Area

Comment on "controlling long-term signaling: Receptor dynamics determine attenuation and refractory behavior of the TGF-b pathway"-Smad2/3 activity does not predict the dynamics of transcription

Cornell Affiliated Author(s)
Author
A. Warmflash
Q. Zhang
A.H. Brivanlou
E.D. Siggia
Abstract

The transforming growth factor-b (TGF-b) pathway plays a fundamental role in development and disease. Despite its importance, the dynamics of signaling activity downstream of ligand stimulation have remained largely unexplored. The recent study by Vizán et al. demonstrates that loss of signaling-capable receptors from the cell surface leads to a refractory period during which cells are incapable of responding to additional signals.

Journal
Science Signaling
Date Published
Research Area

A method to recapitulate early embryonic spatial patterning in human embryonic stem cells

Cornell Affiliated Author(s)
Author
A. Warmflash
B. Sorre
F. Etoc
E.D. Siggia
A.H. Brivanlou
Abstract

Embryos allocate cells to the three germ layers in a spatially ordered sequence. human embryonic stem cells (hescs) can generate the three germ layers in culture; however, differentiation is typically heterogeneous and spatially disordered. We show that geometric confnement is suffcient to trigger self-organized patterning in hescs. in response to BmP4, colonies reproducibly differentiated to an outer trophectoderm-like ring, an inner ectodermal circle and a ring of mesendoderm expressing primitive-streak markers in between.

Journal
Nature Methods
Date Published
Funding Source
R01GM101653
R01HD032105
PHY-0954398
Research Area