Anselmi, C. | Search bioRxiv

bioRxiv2018

A Notch-regulated proliferative stem cell zone in the developing spinal cord is an ancestral vertebrate trait

Vertebrates have evolved the most sophisticated nervous systems we know. These differ from the nervous systems of invertebrates in several ways, including the evolution of new cell types, and the emergence and elaboration of patterning mechanisms to organise cells in time and space. Vertebrates also generally have many more cells in their central nervous systems than invertebrates, and an increase in neural cell number may have contributed to the sophisticated anatomy of the brain and spinal cord. Here we study how increased cell number evolved in the vertebrate central nervous system, investigating the regulation of cell proliferation in lampreys as basally-diverging vertebrate, and focusing on the spinal cord because of its relatively simple anatomy. Markers of proliferating cells show that a medial proliferative progenitor zone is found throughout the lamprey spinal cord. We show that inhibition of Notch signalling disrupts the maintenance of this proliferative zone. When Notch signalling is blocked progenitor cells differentiate precociously, the proliferative medial zone is lost, and differentiation markers activate throughout the medial-lateral axis of the spinal cord. Comparison to other chordates suggests that the emergence of a persistent Notch-regulated proliferative progenitor zone in the medial spinal cord of vertebrate ancestors was a critical step for the evolution of the vertebrate spinal cord and its complexity.\n\nSummary statementVertebrates develop nervous systems with numerous cells. Study of cell proliferation in the lamprey nervous system links this to a medial proliferation zone regulated by Notch signalling, a vertebrate innovation.

evolutionary biology↗

bioRxiv2018

Mitochondrial ATP synthase dimers spontaneously self-associate driven by a long-ranged membrane-induced force

ATP synthases populate the inner membranes of mitochondria, where they produce the majority of the ATP required by the cell. Cryo-electron tomograms of these membranes from yeast to vertebrates have consistently revealed a very precise organization of these enzymes. Rather than being scattered throughout the membrane, the ATP synthases form dimers, and these dimers are organized into rows that extend for hundreds of nanometers. These rows are only observed in the membrane invaginations known as cristae, specifically along their sharply curved edges. Although the presence of these macromolecular structures has been irrefutably linked to the proper development of cristae morphology, it has been unclear what drives the formation of the rows and why they are specifically localized in the cristae. We present the result of a quantitative molecular-simulation analysis that strongly suggests that the ATP synthase dimers organize into rows spontaneously, driven by a long-ranged attractive force that results from relief in the overall elastic strain of the membrane. This strain is caused by the V-like shape of the dimers, unique among membrane-protein complexes, which induces a strong deformation in the surrounding membrane. The process of row formation is therefore not a result of protein-protein interactions, or of a specific lipid composition of the membrane. We further hypothesize that once assembled, the ATP synthase dimer rows prime the inner mitochondrial membrane to develop folds and invaginations, by causing macroscopic membrane ridges that ultimately become the cristae edges. In this view, mitochondrial ATP synthases would contribute to the generation of a morphology that maximizes the surface area of the inner membrane, and thus ATP production. Finally, we outline the key experiments that would be required to verify or refute this hypothesis.

biophysics↗