Biology subjects

van Impel, A.

Publications and source records attributed to van Impel, A..

3 recordsLinked to original sources

bioRxiv2025

The protein-tyrosine phosphatase Shp2 is essential for lymphatic endothelial cell differentiation in zebrafish

Mutations in genes associated with the VEGFC/VEGFR3 signaling pathway are strongly linked to a range of developmental and functional defects in the lymphatic system. PTPN11 encodes SHP2, a protein-tyrosine phosphatase that plays a critical role in receptor protein-tyrosine kinase (RTK) signaling. In this study, we investigated lymphangiogenesis in mutant zebrafish embryos lacking functional Shp2 and demonstrate that Shp2 is essential for normal lymphatic development in the trunk and head regions of zebrafish embryos. Embryos lacking functional Shp2 failed to develop lymphatic vessels and lymphatic endothelial cells (LECs), whereas venous intersegmental vessel (vISV) formation remained unaffected. While endothelial cells sprouted normally from the posterior cardinal vein (PCV), they did not migrate to the horizontal myoseptum to form parachordal lymphangioblast (PL) cells. Rescue experiments using Shp2 mutants demonstrated that catalytic activity and signaling properties of Shp2 are required for restoration of normal lymphangiogenesis. These findings highlight a pivotal role for Shp2 signaling in the migration and differentiation of lymphatic endothelial cells without affecting venous angiogenesis.

developmental biology↗

bioRxiv2022

Neural plate progenitors give rise to both anterior and posterior pituitary cells

The pituitary is the master neuroendocrine gland, which regulates body homeostasis. It consists of the anterior pituitary/adenohypophysis (AH), which harbors hormones producing cells and the posterior pituitary/neurohypophysis (NH), which relays the direct passage of hormones from the brain to the periphery. It is widely accepted that the AH originates from the oral ectoderm (Rathkes pouch) whereas the neural ectoderm contributes to the NH. Using single cell transcriptomics of the zebrafish pituitary we characterized cyp26b1-positive pituicyte of the NH and prop1-positive adenohypophyseal progenitors. We found that these cell types expressed common markers implying lineage relatedness. Genetic tracing revealed that in contrast to the prevailing dogma, neural plate precursors of both zebrafish (her4.3+) and mouse (Sox1+) contribute to both the neurohypophyseal and adenohypophyseal cells. We further show that pituicytes and prop1+ progenitors reside in close anatomical proximity and pituicyte-derived RA-degrading enzyme Cyp26b1 fine-tunes differentiation of prop1+ progenitors into hormone-producing cells. These results challenge the notion that AH cells are exclusively derived from non-neural ectoderm and demonstrate that a cross-talk between neuro- and adeno-hypophyseal cells fine-tunes the development of pituitary neuroendocrine cells.

developmental biology↗

bioRxiv2019

Meningeal lymphatic endothelial cells fulfill scavenger endothelial cell function and employ Mrc1a for cargo uptake

Brain lymphatic endothelial cells (BLECs) constitute a group of loosely connected endothelial cells within the meningeal layer of the zebrafish brain. We previously reported that BLECs efficiently endocytose extracellular cargo molecules (van Lessen et al., 2017), but how this is accomplished and controlled on the molecular level remains unclear. We here compare BLECs to scavenging endothelial cells (SECs) in the embryonic cardinal vein and find them to accept an identical set of substrate molecules. While there is redundancy in the type of scavenger receptors being used, the two cell populations rely for specific substrate molecules on different cell surface receptors to mediate their physiological role: Stab2 appears more critical within SECs in the cardinal vein, while BLECs depend more on the Mrc1a receptor for internalization of cargo. Given the striking similarities to the substrate specificity of cardinal vein SECs, we postulate that BLECs qualify functionally as SECs of the brain.

developmental biology↗