Biology subjects

Buescher, M.

Publications and source records attributed to Buescher, M..

3 recordsLinked to original sources

bioRxiv2021

Mechanism of riboregulation of p62 protein oligomerisation by vault RNA1-1 in selective autophagy

Macroautophagy ensures the clearance of intracellular substrates ranging from single ubiquitinated proteins to large proteotoxic aggregates and defective organelles. The selective autophagy receptor p62 binds these targets and recruits them to double-membrane vesicles, which fuse with lysosomes to degrade their content. We recently uncovered that p62 function is riboregulated by the small non-coding vault RNA1-1. Here, we present detailed insight into the underlying mechanism. We show that the PB1 domain and adjacent linker region of p62 (aa 1-122) are necessary and sufficient for specific vault RNA1-1 binding, and identify lysine 7 and arginine 21 as key hinges for p62 riboregulation. Chemical structure probing of vault RNA1-1 further reveals a central flexible loop within the RNA that mediates the specific p62 interaction. Our data define molecular determinants that govern mammalian autophagy via the p62-vault RNA1-1 riboregulatory pair.

molecular biology↗

bioRxiv2020

Shaking hands is a putative terminal selector and controls axon outgrowth of central complex neurons in the insect model Tribolium

Individual cell types are specified by transcriptional programs which act during development. Gene regulatory mechanisms which specify subtype identity of central complex (CX) neurons are the subject of intense investigation. The CX is a compartment within the brain common to all insect species. The CX functions as a "command center" by initiating motor actions in response to incoming information. The CX is made up of several thousand neurons with more than 60 morphologically distinct identities. Accordingly, transcriptional programs must effect the specification of at least as many neuronal subtypes. Here we demonstrate a role for the transcription factor Shaking hands (Skh) in the specification of embryonic CX neurons in Tribolium. The developmental dynamics of Tc-skh expression are characteristic for terminal selectors of neuronal subtype identity. In the embryonic brain Tc-skh expression is restricted to a subset of neurons, many of which survive to adulthood and contribute to the mature CX. Tc-skh expression is maintained throughout the lifetime of the respective CX neurons. Tc-skh knock-down results in severe axon outgrowth defects thus preventing the formation of an embryonic CX primordium. The as yet unstudied Drosophila skh shows a similar embryonic expression pattern suggesting that subtype specification of CX neurons may be conserved.

developmental biology↗

bioRxiv2019

An ancestral apical brain region contributes to the central complex under the control of foxQ2 in the beetle Tribolium castaneum

The genetic control of anterior brain development is highly conserved throughout animals. For instance, a conserved anterior gene regulatory network specifies the ancestral neuroendocrine center of animals and the apical organ of marine organisms. However, its contribution to the brain in non-marine animals has remained elusive. Here, we study the function of the Tc-foxQ2 forkhead transcription factor, a key regulator of the anterior gene regulatory network of insects. We characterized four distinct types of Tc-foxQ2 positive neural progenitor cells based on differential co-expression with Tc-six3/optix, Tc-six4, Tc-chx/vsx, Tc-nkx2.1/scro, Tc-ey, Tc-rx and Tc-fez1. An enhancer trap line built by genome editing marked Tc-foxQ2 positive neurons, which projected through the primary brain commissure and later through a subset of commissural fascicles. Eventually, they contributed to the central complex. Strikingly, in Tc-foxQ2 RNAi knock-down embryos the primary brain commissure did not split and subsequent development of midline brain structures stalled. Our work establishes foxQ2 as a key regulator of brain midline structures, which distinguish the protocerebrum from segmental ganglia. Unexpectedly, our data suggest that the central complex evolved by integrating neural cells from an ancestral anterior neuroendocrine center.\n\nSummary statementAn ancestral neuroendocrine center contributes to the evolution of the central complex. foxQ2 is a gene required for the development of midline structures of the insect brain, which distinguish protocerebrum from segmental ganglia.

developmental biology↗