Orban, T. | bioRxiv Science

bioRxiv2021

PiggyBac Transposable Element-derived 1 controls Neuronal Progenitor Identity, Stress Sensing and mammal-specific paraspeckles

The evolution and functional integration of new genes, especially those that become core to key functions, remains enigmatic. We consider the mammal-specific gene, piggyBac transposable element derived 1 (PGBD1), implicated in neuronal disorders. While it no longer recognises piggyBac transposon-like inverted repeats and transposase functionality having been lost, it has evolved a core role in neural homeostasis. Depletion of PGBD1 triggers accumulation of mammal-specific paraspeckles and neural differentiation. It acts by two modalities, DNA binding and protein-protein interaction. As a transcriptional repressor of (lnc)NEAT1, the backbone of paraspeckles, it inhibits paraspeckle formation in neural progenitor cells (NPCs). At the protein level it is associated with the stress response system, a function partially shared with (lnc)NEAT1. PGBD1 thus presents as an unusual exemplar of new gene creation, being a recently acquired multi-function, multi-modal gene. Mammalian specificity associated with control of a mammal-specific structure implies coevolution of new genes with new functions.

molecular biology↗

bioRxiv2020

The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish

Lymphangiogenesis, the formation of lymphatic vessels is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in zebrafish. We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of a proper trunk lymphatic network and leading to edema development. We show that Sorbs1 is probably not part of the Vegfc signaling, but instead might interacts with the BMP pathways. Mechanistically, we show that Sorbs1 controls FAK/Src signaling to impact on Rac1 and RhoA GTPases-regulated cytoskeleton processes. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contact rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. Our data thus establish Sorbs1 as an important regulator of lymphangiogenesis distinct from the Vegfc signaling axis, increasing our understanding of context-specific vascular and lymphatic development.

developmental biology↗