Biology subjects

Torres-Paz, J.

Publications and source records attributed to Torres-Paz, J..

6 recordsLinked to original sources

bioRxiv2026

A cellular atlas of Astyanax mexicanus embryogenesis reveals principles of developmental microevolution

The evolution of development is the primary mechanism by which morphological and functional diversity is generated. Comparing the developmental trajectories of single cells in entire embryos across species can reveal how gene expression is conserved and varies, as well as the molecular mechanisms underlying how cell- and tissue-specific changes in developmental regulation generate phenotypic differences. However, this perspective has not addressed the mechanisms of small-scale developmental microevolution, i.e, in closely-related species or even within a single species. The fish Astyanax mexicanus, which comes in two forms adapted to distinct environments - the eyed, river-dwelling morph and the eyeless, cave-adapted morph - is a remarkable model with which to investigate the evolution of gene regulation in a single species. Here, we generated and analyzed a single-nucleus RNA-seq atlas of the development of the two Astyanax morphs, from gastrula to swimming larva. Despite extensive changes in gene expression observed in the eight examined stages, for both ubiquitously-expressed and tissue-specific genes, and in both embryonic and extra-embryonic tissues, the temporal progression of cavefish and surface fish cells was similar in ordinal regression-based pseudotime models using 20-100 core genes. However, transcriptome-wide comparisons of gene expression waves revealed massive heterochronic shifts. In cavefish, some tissues had a majority of genes lagging behind in their transcriptional dynamics (e.g. the optic region), while in others, a majority of genes had accelerated dynamics (e.g. the mesoderm), or else, an equivalent number of genes were found in either category (e.g. the endoderm). Furthermore, cell fate acquisition and differentiation were variably affected in different cavefish lineages, with delays of ~6 hours in the retina, ~2 hours in the axial mesoderm and ~none in the extra-embryonic enveloping layer. Thus, cavefish embryos progress as a mosaic of different tissues, or modules, each following its own transcriptional tempo. Because gene expression differential regulation and time shifts were more prevalent in the early stages and gradually diminished throughout development, we propose that cavefish embryos initially undergo strong decanalisation before becoming re-canalized in line with the shared Astyanax developmental program.

developmental biology↗

bioRxiv2026

The retinal pigment epithelium undergoes anisotropic stretching and nuclear size scaling during optic cup morphogenesis in a fish model.

The morphogenesis of the optic cup provides a robust system for studying how two apposed epithelial monolayers with distinct properties fold and stretch in a coordinated manner to form the primordial eye. While much research has been conducted on the temporal dynamics of retinal neuroepithelium invagination, the spatial organization and stretching of the retinal pigment epithelium has received less attention. The fish species Astyanax mexicanus offers a unique model to examine the mechanisms of optic tissue morphogenesis through a comparative lens, as it exhibits natural variation in eye development between its river-dwelling and cave-adapted morphs. Using quantitative 3D imaging of optic cups from both morphs, we found that RPE morphogenesis involves transient, graded, and anisotropic cell stretching that patterns the epithelium during optic cup shaping. Analyses of RPE nuclear spacing and cell morphology showed that tissue stretching gradually increases along the proximo-distal axis, suggesting maximal tension in the elongated distal RPE cells aligned along the optic cup meridians. Furthermore, nuclear volumes and apical surface areas of RPE cells scaled spatially along the same axis, independently of endoreplication. In the cavefish natural mutant, RPE expansion was delayed by over six hours and proximal stretching exhibited altered isotropy, indicative of disrupted temporal coordination and suggesting modified mechanical constraints. These results demonstrate that RPE morphogenesis is a highly heterogeneous process from a spatiotemporal perspective, offering new insights into the study of the biomechanical principles of eye development in vertebrates. Summary statementThis study reveals the emergence of cell morphology gradients within the retinal pigment epithelium during morphogenesis of the eye in two distinct populations of the same species of fish.

developmental biology↗

bioRxiv2022

Evolution of the regulation of developmental gene expression in blind Mexican cavefish

Changes in gene expression regulation during development are considered the main drivers of morphological evolution and diversification. Here, we analysed the embryonic transcriptomes of surface-dwelling and blind cave-adapted morphs of the species Astyanax mexicanus and their reciprocal F1 hybrids at tailbud stage. Comparing gene expression in parents and allelic expression ratios in hybrids, we found that [~]20% of the transcriptome is differentially expressed and that cis-regulatory changes are the main contributors to variations in early developmental gene expression in the two morphs. We provide a list of 108 cis-regulated genes that could contribute to cavefish developmental evolution, and further explore the regulatory mechanisms controlling the cellular and regional expression of rx3, a "master eye gene". Using quantitative embryology approaches after fluorescent in situ hybridisation, cell transplantations and interference with signalling pathways, we show that rx3 cellular levels -controlling optic cell fates-are regulated in cis and in a cell-autonomous manner, whereas the size of rx3 domain -controlling eye size-depends on non-autonomous Wnt signalling. Altogether, we reveal how distinct mechanisms and regulatory modules can regulate developmental gene expression and shape developmental evolution, with negligible contribution of coding mutations.

developmental biology↗

bioRxiv2021

The olfactory organ is a unique site for resident neutrophils in the brain

For decades we have known that the brain "drains" through the subarachnoid space following a route that crosses the cribriform plate to the nasal mucosa and cervical lymph nodes. Yet little is known about the potential role of the olfactory epithelia and associated lymphatic vasculature in the immune response. To better understand the immune response in the olfactory organs we used cell-specific fluorescent reporter lines in dissected, intact adult brains to visualize blood-lymphatic vasculature and neutrophils in the olfactory sensory system. Here we show that the extensive blood vasculature of the olfactory organs is associated with a lymphatic cell type resembling high endothelial venules (HEVs) of the lymph nodes in mammals and a second resembling Mural Lymphatic Endothelial Cells (muLECs) that extended from the brain to the peripheral olfactory epithelia. Surprisingly, the olfactory organs contained the only neutrophil populations observed in the brain. Damage to the olfactory epithelia resulted in a rapid increase of neutrophils within the olfactory organs as well as the appearance of neutrophils in the brain suggesting that neutrophils enter the brain in response to damage. Analysis of cell division during and after damage showed an increase in BrdU labeling in the olfactory epithelia and a subset of the neutrophils. Our results reveal a unique population of neutrophils in the olfactory organs that are associated with an extensive lymphatic vasculature suggesting a dual olfactory-immune function for this unique sensory system. HighlightsO_LIThe olfactory organ is the only region of the brain that contains resident neutrophils in the adult animal. C_LIO_LIDamage to olfactory sensory neurons triggers a rapid mobilization of neutrophils within the olfactory organ and in the central nervous system. C_LIO_LITwo types of lymphatic vasculature resembling Mural Lymphatic Endothelial Cells (muLEC) and High Endothelial Venules (HEV) are present in the olfactory sensory system. C_LIO_LILymphatic vasculature resembling Mural Lymphatic Endothelial Cells (muLEC) wrap the olfactory bulbs and extend across the cribriform plate to olfactory epithelia. C_LI

neuroscience↗

bioRxiv2021

A 3D molecular map of the cavefish neural plate illuminates eyefield organization and its borders in vertebrates

The vertebrate retinas originate from a specific anlage in the anterior neural plate called the eyefield. The eyefield shares its anterior border with the prospective telencephalon and is in contact ventrally and posteriorly with hypothalamic and diencephalic precursors. Eyefield identity is conferred by a set of "eye transcription factors", whose combinatorial expression has not been precisely characterized. Here, we use the dimorphic teleost species Astyanax mexicanus, which develops proper eyes in the wild type and smaller colobomatous eyes in the blind cavefish embryo, to unravel the molecular anatomy of the eyefield and its micro-evolutionary variations in the two Astyanax morphs. Using a series of markers (Rx3, Pax6, CxCr4b, Zic1, Lhx2, Emx3, Nkx2.1), we draw a comparative 3D expression map at the end of gastrulation/onset of neurulation, which highlights hyper-regionalization of the eyefield into sub-territories of distinct sizes, shapes, cell identities and putative fates along the three body axes. We also discover sub-domains within the prospective telencephalon, and we characterize cell identities at the frontiers of the eyefield. Analyses at the tissue scale and single cell level show variations in volumes and shapes of eyefield subdivisions as well as cellular gene expression levels and identity changes in cavefish. The ventro-medial border and the anterior border of the eyefield contain cells co-expressing hypothalamic and telencephalic marker, respectively, in cavefish embryos. Altogether, we provide a new model of eyefield patterning in 3D and suggest a developmental origin for the emergence of the coloboma phenotype in the natural mutant cavefish embryo.

developmental biology↗

bioRxiv2018

Evolution of gastrulation in cavefish: heterochronic cell movements and maternal factors

Sequential developmental events, starting from the moment of fertilization, are crucial for the acquisition of animal body plan. Subtle modifications in such early events are likely to have a major impact in later morphogenesis, bringing along morphological diversification. Here, comparing the blind cave and the surface morphotypes of Astyanax mexicanus fish, we found heterochronies during gastrulation, producing organizer and axial mesoderm tissues with different properties, including differences in expression of dkk1b, that may have contributed to cavefish brain evolution. These variations observed during gastrulation depend fully on maternal factors, whereas later phenotypic differences in neural development became progressively hidden when zygotic genes take the control over development. Transcriptomic analysis of fertilized eggs from both morphotypes and reciprocal F1 hybrids showed a strong and specific maternal signature. Our work strongly suggests that maternal effect genes and developmental heterochronies occurring during gastrulation have impacted morphological brain change during cavefish evolution.

developmental biology↗