Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition.
Dev Cell
; 59(15): 1940-1953.e10, 2024 Aug 05.
Article
de En
| MEDLINE
| ID: mdl-38776925
ABSTRACT
During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable "winning" floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Organoïdes
/
Tube neural
/
Protéine morphogénétique osseuse de type 4
/
Chorde
Limites:
Animals
Langue:
En
Journal:
Dev Cell
Sujet du journal:
EMBRIOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Autriche