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Roig Puiggros, S.

Publications and source records attributed to Roig Puiggros, S..

4 recordsLinked to original sources

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↗

Transplantation reveals birthdate-dependent post-mitotic competence in cortical neurons

Cortical glutamatergic neurons are generated through temporally ordered developmental programs that link neuronal birthdate to laminar position and identity. Yet, because differentiation continues after cell-cycle exit, it remains unclear how far post-mitotic identity can be reshaped by the environment and whether this residual competence varies across neuronal types. Here, we used transplantation to uncouple birthdate from final laminar position by placing newborn neurons in ectopic laminae in the postnatal mouse cortex. E13-born (i.e. deep layer-destined) and E15-born (i.e. superficial layer-destined) donor neurons displayed distinct birthdate-associated molecular programs before transplantation. After grafting into P0 hosts, both populations migrated and settled across cortical layers, enabling comparison across laminar environments. We simultaneously profiled transcriptomic, morphological and electrophysiological neuronal identities using Patch-seq. Transplanted neurons developed pyramidal morphologies and active membrane properties, but their final identity was not imposed by their laminar position. Thus, the postnatal cortex supports integration and maturation but does not impose canonical laminar identity. Critically, neuronal competence was asymmetric across birthdates. E15-born neurons remained committed toward a robust superficial layer neuron-like profile independently of cortical position, whereas E13-born neurons retained a broad, non-canonical differentiation rather than either converging on a deep- or superficial-layer reference state. This is consistent with the wider intrinsic repertoire of early-born neurons, which the postnatal environment does not resolve. Thus, post-mitotic identity is constrained by developmental history in a birthdate-dependent manner, with early- and late-born neurons retaining fundamentally different differentiation potentials after cell-cycle exit.

neuroscience↗

Dual lineage origins of neocortical astrocytes

Astrocytes represent one of the most abundant cell types in the central nervous system, and play an essential role in nearly all aspects of brain functions1. Recent studies have challenged the notion that cortical astrocytes are a uniform population, and have highlighted their diverse characteristics at the morphological, molecular, and functional levels2-5. However, how this diversity originates and establishes during cortical development, remains largely unknown. Using single-cell RNA sequencing, we identified five distinct astrocyte subtypes displaying unique spatial patterns in the mouse neocortex, and discovered essential regulators for their formation. Furthermore, we used TrackerSeq6, a method that integrates heritable DNA barcodes into the genome of electroporated progenitors, to track clonally related astrocytes, and identified two distinct lineages that give rise to the five astrocyte subtypes. The first lineage derives from Emx1+ multipotent progenitors that first generate neurons and then switch to produce cortical astrocytes. The second lineage stems from a fate-restricted progenitor population that exclusively gives rise to a specific subset of cortical astrocytes, marked by Olig2. The knockout of this gene in cortical progenitors is sufficient to promote a fate switch between the two lineages. These findings offer novel insights into the cellular mechanisms underlying astrocyte diversity, highlighting the presence of multiple progenitor subtypes, responsible for generating distinct subtypes of astrocytes.

neuroscience↗

Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements

In human, execution of unimanual movements requires lateralized activation of the primary motor cortex, which then transmits the motor command to the contralateral hand through the crossed corticospinal tract (CST). Mutations in NETRIN-1 alter motor control lateralization, leading to congenital mirror movements. To address the role of midline Netrin-1 on CST development and subsequent motor control, we analyzed the morphological and functional consequences of floor-plate Netrin-1 depletion in conditional knock-out mice (Shh::cre;Ntn1lox/lox mice). Here, we show that depletion of floor plate Netrin-1 critically disrupts midline crossing of the CST, whereas the other commissural systems are mostly preserved. The CST defect results in abnormal but functional ipsilateral projections, and is associated with abnormal symmetric movements. Therefore, our study reveals a new role for Netrin-1 in CST development. It also describes a unique mouse model recapitulating characteristics of human congenital mirror movements, through abnormal CST decussation.

neuroscience↗