Biology subjects

Machon, O.

Publications and source records attributed to Machon, O..

3 recordsLinked to original sources

bioRxiv2025

Cell polarity of neural crest-derived mesenchymal cells controls craniofacial development

Cell polarity is essential for tissue organization during development. While the molecular mechanisms governing epithelial cell polarity are well understood, the polarity of mesenchymal cells remains under debate. Using a mouse model with Wnt5a deletion in cranial neural crest cells, we analyzed polarized intracellular components that regulate mesenchymal cell organization, proliferation, and migration prior to mesenchymal condensation in the craniofacial region. Loss of Wnt5a disrupted the polarized localization of primary cilia and the Golgi apparatus along the proximal-distal axis. This intracellular disorganization impaired the orientation of the cell division plane and was accompanied by a reduced proliferation rate. As a result, several distal facial structures, including the frontonasal cartilage, premaxilla, and distal mandible, were significantly reduced in Wnt5a conditional mutants.

developmental biology↗

bioRxiv2024

Mesenchymal Meis2 controls whisker development independently from trigeminal sensory innervation

Hair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Here we show that Meis2 expression in cells derived from the neural crest is critical for whisker formation, and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factor Foxd1, which is typical of pre-dermal condensation. However, deletion of Foxd1 does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation or Foxd1 expression.

developmental biology↗

bioRxiv2020

MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus

The choroid plexus (ChP) produces cerebrospinal fluid and forms a critical barrier between the brain and the circulation. While the ChP forms in each brain ventricle, it adopts a different shape in each one and remarkably little is known about the mechanisms underlying its development. Here, we show that epithelial WNT5A is critical for determining fourth ventricle (4V) ChP morphogenesis and size. Systemic Wnt5a knockout, or forced WNT5A overexpression beginning at E10.5, profoundly reduced the size and development of ChP in all ventricles. However, conditional deletion of Wnt5a expression in Foxj1-expressing epithelial cells affected only the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical Wnt signaling via Ror1/Ror2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS1 and MEIS2 as upstream regulators of Wnt5a in the 4V ChP epithelium.

developmental biology↗