PUBLICATION
Midkine-a interacts with Ptprz1b to regulate neural plate convergence and midline formation in the developing zebrafish hindbrain
- Authors
- Le, Y., Rajasekhar, K., Loo, T.Y.J., Saunders, T.E., Wohland, T., Winkler, C.
- ID
- ZDB-PUB-250210-2
- Date
- 2025
- Source
- Developmental Biology : (Journal)
- Registered Authors
- Loo, Tricia, Saunders, Timothy Edward, Winkler, Christoph, Wohland, Thorsten
- Keywords
- C-division, Convergence, PCP, fluorescence cross correlation spectroscopy, planar cell polarity, proximity-ligation assay, zebrafish
- MeSH Terms
-
- Animals
- Rhombencephalon*/embryology
- Rhombencephalon*/metabolism
- Cytokines/metabolism
- Receptor-Like Protein Tyrosine Phosphatases, Class 5/genetics
- Receptor-Like Protein Tyrosine Phosphatases, Class 5/metabolism
- Midkine*/genetics
- Midkine*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Cell Polarity*/genetics
- Body Patterning/genetics
- Carrier Proteins/genetics
- Carrier Proteins/metabolism
- Neural Plate*/embryology
- Neural Plate*/metabolism
- Zebrafish*/embryology
- Zebrafish*/metabolism
- Gene Expression Regulation, Developmental
- Mutation
- PubMed
- 39924070 Full text @ Dev. Biol.
Citation
Le, Y., Rajasekhar, K., Loo, T.Y.J., Saunders, T.E., Wohland, T., Winkler, C. (2025) Midkine-a interacts with Ptprz1b to regulate neural plate convergence and midline formation in the developing zebrafish hindbrain. Developmental Biology. :.
Abstract
A midline in the developing central nervous system allows symmetric distribution of neural progenitors that later establish functional, bilaterally symmetric neural circuits. In the zebrafish hindbrain, a midline forms early during neurulation as a result of coordinated cell convergence and midline-crossing cell divisions (C-divisions). These processes are controlled by the Wnt/planar cell polarity (PCP) pathway that positions progenitors close to a presumptive midline to perform C-divisions. Other upstream cues that control the extent of neural plate convergence, however, remain unclear. Midkine (Mdk) and pleiotrophin (Ptn) are structurally related heparin-binding growth factors that are dynamically expressed in the developing hindbrain. We show that two zebrafish Mdks, Mdka and Mdkb, as well as Ptn interact with distinct affinities in vivo with the protein tyrosine phosphatase receptor Ptprz1b. Zebrafish mdka and ptprz1b mutants exhibit impaired neural plate convergence along with misplaced C-divisions, defective cell polarity and transiently duplicated midlines. These defects are absent in mdka; mdkb double mutants suggesting antagonistic roles of Mdka and Mdkb to coordinate convergence and C-divisions. Overexpression of Drosophila Prickle, a key component of the Wnt/PCP pathway, rescued the midline duplications in mdka and ptprz1b mutants that exhibited significantly reduced levels of prickle pk1b, pk2a, and pk2b expression. Ptprz1b overexpression, on the other hand, up-regulated pk2a transcription. Our findings therefore suggest roles for Mdka, Mdkb and Ptprz1b in coordinating neural plate convergence, neural progenitor positioning and midline formation by controlling the levels of prickle expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping