Biology subjects

Amblard, I.

Publications and source records attributed to Amblard, I..

4 recordsLinked to original sources

bioRxiv2026

Temporally distinct CDX programmes preconfigure vagal and trunk neural crest

Neural crest cells (NCCs) are progenitor cells vital in establishing the head, heart, gut and peripheral nervous system of vertebrate embryos. Disruptions to NCC development underlie neurocristopathies, which constitute a wide array of congenital anomalies. Yet how NCCs acquire defined regional identities that enable them to generate distinct derivatives along the body axis remains unclear. Here, we identify an epiblast progenitor population in mouse embryos that transiently contributes to vagal neural crest cells and trunk-to-tail derivatives. Using single-cell spatial transcriptomics across successive stages of neural crest migration, we generate a cervicothoracic cell atlas that resolves vagal and trunk neural crest cells in situ. Combining in vivo lineage tracing with in vitro models of neural crest induction, we show that despite transiently sharing a lineage, vagal and trunk neural crest arise through separate mechanisms. Temporally discrete regionalisation events mediated by CDX transcription factors establish HOX states that define vagal versus trunk identity. These findings revise models of NCC formation by demonstrating that temporally separate epiblast regionalisation events preconfigure neural crest and neural progenitor identities. More broadly, the results suggest that primary regionalisation events coordinately govern multiple cell lineages at the cervicothoracic transition, with implications for understanding neurocristopathies involving combined enteric and trunk derivatives.

developmental biology↗

bioRxiv2024

A dual enhancer-silencer element ensures transient Cdx2 expression during posterior body formation

During development, cells express precise gene expression programmes to assemble the trunk of the body plan. Appropriate control over the duration of the transcription factor Cdx2 is critical to achieve this outcome, yet, how cells control the onset, maintenance or termination of Cdx2, has remained unclear. Here, we delineate the cis-regulatory logic orchestrating dynamic Cdx2 expression in mouse caudal epiblast progenitors and their derivatives - spinal cord and presomitic mesoderm. Combining CRISPR-mediated deletion of regulatory elements with in vitro models and in vivo validation, we demonstrate that distinct enhancers, and a silencer, embedded at the Cdx2 locus, act sequentially to drive transient Cdx2 expression. We pinpoint a minimal silencer element that relies on a nuclear receptor motif to extinguish Cdx2. Changing this single motif converts the repressive element to an enhancer with opposite regulatory behaviour. Our findings elucidate design principles of developmental enhancers and silencers and establish a dual enhancer-silencer cis-regulatory logic ensuring precise spatiotemporal control over gene expression for vertebrate body patterning.

developmental biology↗

bioRxiv2021

Reciprocal regulation of Shh trafficking and H2O2 levels via a noncanonical BOC-Rac1 pathway

Among molecules that bridge environment, cell metabolism, and cell signaling, H2O2 recently appeared as an emerging but central player. Its level depends on cell metabolism and environment and was recently shown to play key roles during embryogenesis, contrasting with its long-established role in disease progression. We decided to explore whether the secreted morphogen Sonic hedgehog (Shh), known to be essential in a variety of biological processes ranging from embryonic development to adult tissue homeostasis and cancers, was part of these interactions. Here, we report that H2O2 levels control key steps of Shh delivery and that physiological in vivo modulation of H2O2 levels changes Shh distribution and tissue patterning. A feedback loop exists in which Shh trafficking controls H2O2 synthesis via a non-canonical BOC-Rac1 pathway, leading to cytoneme growth. Our findings reveal that Shh directly impacts its own distribution, thus providing a molecular explanation for the robustness of morphogenesis to both environmental insults and individual variability.

cell biology↗

bioRxiv2020

Bidirectional transfer of Engrailed homeoprotein across the plasma membrane requires PIP2

1.Homeoproteins are a class of transcription factors sharing the unexpected property of intercellular trafficking. It confers to homeoproteins a paracrine mode of action, shown to exert a wide range of physiological functions, during development and in the adult. Internalization and secretion, the two steps of intercellular transfer, rely on unconventional mechanisms but the cellular mechanisms at stake still need to be fully characterized. Thanks to the design of new quantitative and sensitive assays dedicated to the study of homeoprotein transfer in cell culture, we demonstrate a core role of the phosphoinositides PIP2 together with cholesterol in the translocation of Engrailed2 (EN2) homeoprotein across the plasma membrane. Both secretion and internalization are regulated according to PIP2 levels, challenged by drug or enzymatic treatments. In addition, EN2 specifically interacts with PIP2 and the reduced affinity of a paracrine deficient mutant of EN2 supports a role of PIP2 in homeoprotein physiological function. We propose that the two ways plasma membrane translocation steps accounting for homeoprotein secretion and internalization respectively are parts of a common process. Summary StatementDeciphering the mechanism of homeoprotein intercellular trafficking

cell biology↗