IN VIVO ANALYSIS OF MIDKINE/PLEIOTROPHIN RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE ZETA 1 INTERACTIONS AND FUNCTIONS IN ZEBRAFISH EMBRYOGENESIS

Abstract

The formation of a midline in the central nervous system ensures bilaterally symmetric distribution of neural progenitors and circuits. In zebrafish, midline formation is orchestrated by morphogenetic signalling, cell convergence and midline-crossing cell divisions (C-divisions). Which factors coordinate these processes remained poorly understood. Here, I showed that the heparin-binding growth factors midkine (Mdk) and pleiotrophin (Ptn) play essential roles in midline formation. I demonstrated that in zebrafish Mdka, Mdkb and Ptn interact with two receptor-type protein tyrosine phosphatases, Ptprz1a and Ptprz1b, in vivo. Further, I generated zebrafish mutants and showed that Mdka-Ptprz1b is essential for cell migration, convergence and C-divisions to facilitate midline formation in the hindbrain. I identified that Mdka-Ptprz1b acts upstream of prickle, a key Wnt/planar cell polarity (PCP) component. Together, my findings suggest that Mdka-Ptprz1b controls Wnt/PCP signalling to coordinate neural progenitor positioning and polarity of cell divisions to establish bilateral symmetry in the developing zebrafish hindbrain.