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Colle, C.

Publications and source records attributed to Colle, C..

4 recordsLinked to original sources

Molecular basis of competence for neural induction in the chick embryo

Competence is the capacity of a cell or tissue to respond to a specific inducing signal from a neighbouring tissue, by changing its fate in a specific direction. Neural induction is the process by which the epiblast of the early embryo responds to signals from the organizer (the tip of the primitive streak in amniotes) by forming a neural plate. Here we study why three regions of the early chick embryo lack competence to respond to neural induction by a grafted organizer: the outer anterior area opaca and the posterior area opaca at primitive streak stages (HH3+-4-), and the inner anterior area opaca at head process stage (HH5), in comparison with the competent anterior inner area opaca at HH3+-4-.Molecular analysis of these tissues, and their temporal dynamics following exposure to the organizer, reveals several differences. Among them, increased BMP and decreased ERK signalling characterise the non-competent regions. Inhibition of BMP can restore competence to HH5 epiblast; a combination of BMP-inhibition with ERK-stimulation by FGF8 can confer competence to the outer area opaca, whereas none of these can endow posterior epiblast with competence for neural induction. We conclude that spatiotemporal competence of epiblast for neural induction is regulated by several mechanisms, including extracellular signals.

developmental biology↗

The organizer as a cooperative of signaling cells for neural induction

The "organizer", discovered 100 years ago by Hans Spemann and Hilde Mangold, is a special region of vertebrate embryos at the gastrula stage; it emits signals that can re-direct the fate of neighboring cells to acquire neural plate identity. It is generally imagined as unique population of cells producing one or a few signaling molecules, responsible for neural induction and for patterning the neural plate and the mesoderm. Here we use single cell and tissue transcriptomics to explore the expression of signaling molecules in the node (the amniote organizer). Although all organizer cells express the homeobox gene Goosecoid, node cells show a diversity of transcription factor signatures associated with expression of subsets of many signaling molecules, suggesting distinct cell sub-populations. Using a recently described Gene Regulatory Network (GRN) of 175 transcriptional responses to neural induction, we explore the activities of 22 of these signals and find that some of them regulate the expression of components of the GRN that are not responsive to previously described pathways associated with neural induction. These results suggest that rather than a single, static, homogeneous population, the organizer comprises a diverse collective of specialized cells that emit cooperating signals to instruct receiving neighbors to adopt their new identities. Significance StatementThe Spemann-Mangold organizer is an embryonic region that can induce the formation of a fully patterned nervous system from non-neural embryonic cells. Here we show that it is made up of a diversity of cell populations that emit distinct sets of signals, which cooperate to account for the repertoire of molecular responses in receiving cells. Several of these signals had not previously been associated with neural induction or patterning.

developmental biology↗

Direct Reprogramming of Non-limb Fibroblasts toCells with Properties of Limb Progenitors

The early limb bud consists of mesenchymal progenitors (limb progenitors) derived from the lateral plate mesoderm (LPM) that produce most of the tissues of the mature limb bud. The LPM also gives rise to the mesodermal components of the trunk, flank and neck. However, the mesenchymal cells generated at these other axial levels cannot produce the variety of cell types found in the limb bud, nor can they be directed to form a patterned appendage-like structure, even when placed in the context of the signals responsible for organizing the limb bud. Here, by taking advantage of a direct reprogramming approach, we find a set of factors (Prdm16, Zbtb16, and Lin28) normally expressed in the early limb bud, that are capable of imparting limb progenitor-like properties to non-limb fibroblasts. Cells reprogrammed by these factors show similar gene expression profiles, and can differentiate into similar cell types, as endogenous limb progenitors. The further addition of Lin41 potentiates proliferation of the reprogrammed cells while suppressing differentiation. These results suggest that these same four key factors may play pivotal roles in the specification of endogenous limb progenitors.

developmental biology↗

In vivo topology converts competition for cell-matrix adhesion into directional migration

When migrating in vivo, cells are exposed to numerous, and somewhat conflicting, signals: chemokines, repellents, extracellular matrix, growth factors. The roles of several of these molecules have been studied individually in vitro or in vivo but we have yet to understand how cells integrate them. To start addressing this question, we used the cephalic neural crest as a model system and looked at the roles of its best examples of positive and negative signals: stromal-cell derived factor 1 (Sdf1/Cxcl12) and class3-Semaphorins. Our results indicate that Sdf1 and Sema3A antagonistically control cell-matrix adhesion via opposite effects on Rac1 activity at the single cell level. Directional migration at the population level emerges as a result of global Semaphorin-dependent confinement and broad activation of adhesion by Sdf1 in the context of a biased Fibronectin distribution. These results indicate that uneven in vivo topology renders the need for precise distribution of secreted signals mostly dispensable.

developmental biology↗