Biology subjects

Camacho-Aguilar, E.

Publications and source records attributed to Camacho-Aguilar, E..

6 recordsLinked to original sources

bioRxiv2026

Measuring developmental information encoded by a dynamicallandscape

During embryogenesis, as cells proliferate and assemble into tissues, they undergo a sequence of transitions between distinct molecular states eventually giving rise to a cellular population consisting of an appropriate distribution of specific functional cell types. Recent progress on the dynamics underlying decision-making in developmental landscape makes it feasible to start analysing the amount of information involved in constructing such systems. To explore this we introduce the notion of potency of a developmental landscape and attempt to calculate it for two development systems of current interest, in-vitro differentiation of epiblast-like cells into neural and mesodermal progenitors and the worm vulva patterning system. Our approach integrates concepts from developmental biology, information theory and dynamical systems to estimate both the number and identity of signalling regimes that give rise to distinguishable temporal response patterns.

developmental biology↗

bioRxiv2025

Juxtaposition of human pluripotent stem cells with amnion-like cells is sufficient to trigger primitive streak formation

Studies in the mouse have established that communication between the trophectoderm and the epiblast is crucial for initiating gastrulation. In the primate embryo, the amnion rather than the trophectoderm is directly juxtaposed to the epiblast and may play this role. To model the interactions between the amnion and epiblast, we differentiated human pluripotent stem cells (hPSCs) to amnion-like cells (AMLCs) and juxtaposed them in a controlled manner with undifferentiated hPSCs, which represent the epiblast. We found that juxtaposition between these cell types is sufficient to initiate a range of cell behaviors associated with gastrulation including organized differentiation to primitive streak and downstream mesendodermal cell fates and directed cell migration out of the primitive streak region. Performing knockout experiments specifically in either the epiblast or amnion compartment revealed intricate crosstalk that is required to properly initiate gastrulation. In particularly, using knockouts of NODAL we show that Nodal signaling in both the amnion and epiblast is required for gastrulation patterning. Finally, we show that inductive ability is a transient property acquired during amnion differentiation, and that cells that differentiate from this inductive state acquire an extraembryonic mesenchyme identity. This study establishes a system to study epiblast-amnion communication and shows that this communication is sufficient to initiate gastrulation in the epiblast.

developmental biology↗

bioRxiv2024

Endogenous Nodal switches Wnt interpretation from posteriorization to germ layer differentiation in geometrically constrained human pluripotent cells

The Wnt pathway is essential for inducing the primitive streak, the precursor of the mesendoderm, as well as setting anterior-posterior coordinates. How Wnt coordinates these diverse activities remains incompletely understood. Here, we show that in Wnt-treated human pluripotent cells, endogenous Nodal signaling is a crucial switch between posteriorizing and primitive streak-including activities. While treatment with Wnt posteriorizes cells in standard culture, in micropatterned colonies, higher levels of endogenously induced Nodal signaling combine with exogenous Wnt to drive endoderm differentiation. Inhibition of Nodal signaling restores dose-dependent posteriorization by Wnt. In the absence of Nodal inhibition, micropatterned colonies undergo spontaneous, elaborate morphogenesis concomitant with endoderm differentiation even in the absence of added extracellular matrix proteins like Matrigel. Our study shows how Wnt and Nodal combinatorially coordinate germ layer differentiation with AP patterning and establishes a system to study a natural self-organizing morphogenetic event in in vitro culture.

developmental biology↗

bioRxiv2022

Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

Secreted morphogen signals play a key role in the determination of cell fates during embryonic development. BMP signaling is essential for mammalian gastrulation, as it initiates a cascade of signals that controls the self-organized patterning of the three germ layers. Although morphogen signals are typically thought to induce cell fates in a concentration-dependent manner, development is a highly dynamic process, so it is crucial to understand how time-dependent signaling affects cellular differentiation. Here we show that varying the duration of BMP signaling in human pluripotent stem cells (hPSCs) leads to either cells remaining pluripotent, or differentiating to mesodermal or extraembryonic states, while varying the concentration does not cause efficient mesodermal differentiation at any dose. Thus, there is a morphogen effect in time but not in concentration, and an appropriately timed pulse of BMP induces hPSCs to a mesodermal fate more efficiently than sustained signaling at any concentration. Using live cell imaging of signaling and cell fate reporters together with a simple mathematical model, we show that this effect is due to a combinatorial interpretation of the applied BMP signal and induced endogenous WNT signaling. Our findings have implications for how signaling pathways control the landscape of early human development.

developmental biology↗

bioRxiv2021

A quantitative landscape of cell fate transitions identifies principles of cellular decision-making

Fate decisions in developing tissues involve cells transitioning between a set of discrete cell states, each defined by a distinct gene expression profile. Geometric models, often referred to as Waddington landscapes, in which developmental paths are given by the gradient and cell states by the minima of the model, are an appealing way to describe differentiation dynamics and developmental decisions. To construct and validate accurate dynamical landscapes, quantitative methods based on experimental data are necessary. To this end we took advantage of the differentiation of neural and mesodermal cells from pluripotent mouse embryonic stem cells exposed to different combinations and durations of signalling factors. We developed a principled statistical approach using flow cytometry data to quantify differentiating cell states. Then, using a framework based on Catastrophe Theory and approximate Bayesian computation, we constructed the corresponding dynamical landscape. The result was a quantitative model that accurately predicted the proportions of neural and mesodermal cells differentiating in response to specific signalling regimes. Analysis of the geometry of the landscape revealed two distinct ways in which cells make a binary choice between one of two fates. We discuss the biological relevance of these mechanisms and suggest that they represent general archetypal designs for developmental decisions. Taken together, the approach we describe is broadly applicable for the quantitative analysis of differentiation dynamics and for determining the logic of developmental cell fate decisions.

developmental biology↗

bioRxiv2021

Quantifying cell transitions in C. elegans with data-fitted landscape models

Increasing interest has emerged in new mathematical approaches that simplify the study of complex differentiation processes by formalizing Waddingtons landscape metaphor. However, a rational method to build these landscape models remains an open problem. Building on pioneering work by Corson and Siggia (2012, 2017) we study vulval development in C. elegans by developing a framework based on Catastrophe Theory (CT) and approximate Bayesian computation (ABC) to build data-fitted landscape models. We first identify the candidate qualitative landscapes, and then use CT to build the simplest model consistent with the data, which we quantitatively fit using ABC. The resulting model suggests that the underlying mechanism is a quantifiable two-step decision controlled by EGF and Notch-Delta signals, where a non-vulval/vulval decision is followed by a bistable transition to the two vulval states. This new model fits a broad set of data and makes several novel predictions.

developmental biology↗