Daniel Aguilar-Hidalgo

University of British Columbia | UBC · Biomedical Research Centre (BRC)

We present a theory of pattern formation in growing domains inspired by biological examples of tissue development. Gradients of signaling molecules regulate growth, while growth changes these graded chemical patterns by dilution and advection. We identify a critical point of this feedback dynamics, which is characterized by spatially homogeneous gr...

Patterning and growth are linked during early development and have to be tightly controlled to result in a functional tissue or organ. During the development of the Drosophila eye, this linkage is particularly clear: the growth of the eye primordium mainly results from proliferating cells ahead of the morphogenetic furrow (MF), a moving signaling w...

During organ development, the progenitor state is transient, and depends on specific combinations of transcription factors and extracellular signals. Not surprisingly, abnormal maintenance of progenitor transcription factors may lead to tissue overgrowth, and the concurrence of signals from the local environment is often critical to trigger this ov...

The morphology and function of organs depend on coordinated changes in gene expression during development. These changes are controlled by transcription factors, signaling pathways, and their regulatory interactions, which are represented by gene regulatory networks (GRNs). Therefore, the structure of an organ GRN restricts the morphological and fu...

During development, extracellular signaling molecules interact with intracellular gene networks to control the specification, pattern and size of organs. One such signaling molecule is Hedgehog (Hh). Hh is known to act as a morphogen, instructing different fates depending on the distance to its source. However, how Hh, when signaling across a cell...

The emergence of the anterior-posterior body axis during early gastrulation constitutes a symmetry-breaking event, which is key to the development of bilateral organisms, and its mechanism remains poorly understood. Two-dimensional gastruloids constitute a simple and robust framework to study early developmental events in vitro. Although spontaneou...

The mechanism by which morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. Here, we developed a minimal gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage commitment and embedded it into “cellular” agents that respond to a dynamic morphogen...

Morphogen gradients are fundamental to establish morphological patterns in developing tissues¹. During development, gradients scale to remain proportional to the size of growing organs2,3. Scaling is a universal gear adjusting patterns to size in living organisms3–8, yet its mechanisms remain unclear. Here, focusing on the Dpp gradient in the Droso...

Small Open Reading Frames (smORFs) coding for peptides of less than 100 amino-acids are an enigmatic and pervasive gene class, found in the tens of thousands in metazoan genomes. Here we reveal a short 80 amino-acid peptide (Pegasus) which enhances Wingless/Wnt1 protein short-range diffusion and signalling. During Drosophila wing development, Wingl...

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL , a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs provide an...

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs allow simul...

The emergence of germ layers in embryos during gastrulation is a key developmental milestone. How morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. To understand this, we developed a gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage comm...

In vitro models of postimplantation human development are valuable to the fields of regenerative medicine and developmental biology. Here, we report characterization of a robust in vitro platform that enabled high-content screening of multiple human pluripotent stem cell (hPSC) lines for their ability to undergo peri-gastrulation–like fate patterni...

Small Open Reading Frames (smORFs) coding for peptides of less than 100 amino-acids are emerging as a fundamental and pervasive gene class, found in the hundreds of thousands in metazoan genomes. Even though some of these genes are annotated in the genome, their function, if any, remains unknown. Here we characterize the function of a smORF encodin...

Morphogens are secreted signaling molecules that mediate tissue patterning and growth of embryonic tissues. They are secreted in a localized region and spread through the tissue to form a graded concentration profile. We present a cell-based model of morphogen spreading that combines secretion in a local source, extracellular diffusion and cellular...

We present a theory of pattern formation in growing domains inspired by biological examples of tissue development. Gradients of signaling molecules regulate growth, while growth changes these graded chemical patterns by dilution and advection. We identify a critical point of this feedback dynamics, which is characterized by spatially homogeneous gr...

One of the most intriguing aspects in developing tissues is the emergence of chemical patterns with the capability to drive cellular differentiation, provide positional information and stimuli or inhibit growth. Among these features, the study of cell specificity driven by chemical patterns requires the coupling of positional information mechanisms...

A fundamental question in developmental biology is how organ size is controlled. We have previously shown that the area growth rate in the Drosophila eye primordium declines inversely proportionally to the increase in its area. How the observed reduction in the growth rate is achieved is unknown. Here, we explore the dilution of the cytokine Unpair...

The morphology and function of organs depend on coordinated changes in gene expression during development. These changes are controlled by transcription factors, signaling pathways and their regulatory interactions, which are represented by gene regulatory networks (GRNs). Therefore, the structure of an organ GRN restricts the morphological and fun...

How a developing organ grows and patterns to its final shape is an important question in developmental biology. Studies of growth and patterning in the Drosophila wing imaginal disc have identified a key player, the morphogen Decapentaplegic (Dpp). These studies provided insights into our understanding of growth control and scaling: expansion of th...

Dynamical interactions among sets of genes (and their products) regulate developmental processes and some dynamical diseases, like cancer. Gene regulatory networks (GRNs) are directed networks that define interactions (links) among different genes/proteins involved in such processes. Genetic regulation can be modified during the time course of the...

During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze...

We analyze a distributed information network in which each node has access to the information contained in a limited set of nodes (its neighborhood) at a given time. A collective computation is carried out in which each node calculates a value that implies all information contained in the network (in our case, the average value of a variable that c...

The process of CO oxidation on Pt(100) at low pressure has a complicated behavior by spontaneously reconfiguring the structure of the surface (1 × 1) to a quasi-hexagonal (hex). The interface between the empty hex surface and chemisorbed O allows its diffusion under the layer of platinum atoms. Either on the stage of subsurface oxygen formation or...

Gene regulatory networks set a second order approximation to genetics understanding, where the first order is the knowledge at the single gene activity level. With the increasing number of sequenced genomes, including humans, the time has come to investigate the interactions among myriads of genes that result in complex behaviors. These characteris...

Gene regulatory networks are one of the most important goals in the novel discipline of system biology. These regulatory networks, through the interaction of multi-ple genes, control and guide the proteic interactions and, in fact, the cellular behaviour. Understanding this regulation is, therefore, essential in the investigation in organogenesis,...