As of 2024, our group has joined the MoPED team, co-directed by Anne Barlier and Heather Etchevers.
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Heather's group studies how certain kinds of birth defects occur, called congenital neurocristopathies. The palate, eyes and/or heart are frequently affected, but dozens of rarer diseases also present symptoms in the skin, gut or the nervous system. While the genetic bases of many specific neurocristopathies over the last decade have been found, most remain without molecular diagnosis and are relatively poorly defined as clinical entities due to their diverse presentations and rarity.
A subset of malformation syndromes are associated with genetic variants also found in many adult cancers. The result in survivors is inappropriate growth factor signaling, leading to effects on decisions in stem cell identities and tissue growth. The resulting organism is a mosaic of affected (mutated) and unaffected (non-mutated) cells. Their interactions during development can lead to diseases that appear very different from, but are mechanistically related to and sometimes predispose to, certain cancers.
Mouse models used by our group phenocopy (reproduce many aspects of) syndromes found in human fetuses or children. Characterizing these models and understanding the mechanisms of their outcomes should lead to improved diagnoses in relevant patient cohorts and new therapeutic approaches by repurposing drugs used in targeted chemotherapies.
Genetic causes and modifiers of giant congenital melanocytic nevus
Dr. Daniel Aldea, a senior postdoctoral scientist now a member of the Okinawa Institute of Science and Technology, worked on this project from 2023-2026 as part of the EU-funded MELCAYA consortium.
The large and giant congenital melanocytic nevus (CMN) is a visibly conspicuous malformation of the skin, present at birth. It can present as a restricted, stable and benign tumor, or be associated in syndromic form with additional cutaneous, neurological or oncological symptoms.
We study the effects of the molecular signaling pathways shown to be present in CMN in the embryological precursors to pigment cells using multiple systems:
- Surgical and pathology specimens from large congenital melanocytic nevi (CMN)
- Induced pluripotent stem cells from human CMN
- Comparative transcriptomics in primary cultures of mouse cells from neural crest-specific induction of constitutively active BRAF or NRAS mutations
- Phenotypic characterization of mouse models with different onset or compartments of BRAF or NRAS mutations during prenatal and postnatal development, in order to understand cell non-autonomous effects in CMN syndrome and related disorders
Intracellular effectors of vascular and craniofacial malformations
Somatic mutations in genes encoding one or more effectors of the RAS-RAF and PI3K signaling pathways, and propagated in the cellular components of blood vessels, cause rare, defiguring and sometimes lethal vascular malformations. Dr. Elise Marechal, during her Ph.D. work with us, helped delineate many of these phenotypes.
Our transgenic mouse and human cellular models for the expression of such mutations in neural crest lineages implicates these signaling pathways not only in vascular but also craniofacial malformations affecting the skull and palate, in progressive peripheral neuropathies (see 2025 preprint on bioRxiv, submitted for 2026 publication), and in neuroendocrine disorders.
Human Developmental Cell Atlas
This national consortium project launched just before the COVID-19 pandemic with the Zaffran group. It entailed mapping the specific transcriptomic signatures of each cell in the developing human body in order to better understand normal and disease-associated physiology during prenatal life. We introduced new technologies to the GBiM platform and contributed unprecedently detailed data on the cellular composition of the first-trimester heart as it turns from a primordium into a functional and vital organ. This data contributes to the international Human Cell Atlas effort and was published, with a cover illustration, in the journal Development in 2025.
