Biology subjects

Mann, R. S.

Publications and source records attributed to Mann, R. S..

3 recordsLinked to original sources

bioRxiv2018

Stereotyped Terminal Axon Branching of Leg Motor Neurons Mediated by IgSF Proteins DIP-α and Dpr10

The ability of animals to perform coordinated movements depends on the precise organization of neural circuits controlling motor function. Motor neurons (MNs), which are key components of these circuits, must project their axons out of the central nervous system and form precise terminal branching patterns at specific muscles in the periphery. By focusing on the Drosophila adult leg neuromuscular system we show that the stereotyped terminal branching of a subset of leg MNs is mediated by interacting transmembrane Ig superfamily (IgSF) proteins DIP- and Dpr10, present in MNs and target muscles, respectively. Importantly, the DIP-/Dpr10 interaction is needed only after MN axons reach the vicinity of their muscle targets. Live imaging of this process suggests that precise terminal branching patterns are gradually established by DIP-/Dpr10-dependent interactions between fine axon filopodia and developing muscles. Further, different leg MNs depend on the DIP- and Dpr10 interaction to varying degrees that correlate with the morphological complexity of the MNs and their muscle targets, suggesting that some MNs depend upon multiple sets of interacting proteins to establish terminal axon branching.

neuroscience↗

bioRxiv2018

cis-regulatory architecture of a short-range EGFR organizing center in the Drosophila melanogaster leg.

We characterized the establishment of an Epidermal Growth Factor Receptor (EGFR) organizing center (EOC) during leg development in Drosophila melanogaster. Initial EGFR activation occurs in the center of leg discs by expression of the EGFR ligand Vn and the EGFR ligand-processing protease Rho, each through single enhancers, vnE and rhoE, that integrate inputs from Wg, Dpp, Dll and Sp1. Deletion of vnE and rhoE eliminates vn and rho expression in the center of the leg imaginal discs, respectively. Animals with deletions of both vnE and rhoE (but not individually) show distal but not medial leg truncations, suggesting that the distal source of EGFR ligands acts at short-range to only specify distal-most fates, and that multiple additional ring enhancers are responsible for medial fates. Further, based on the cis-regulatory logic of vnE and rhoE we identified many additional leg enhancers, suggesting that this logic is broadly used by many genes during Drosophila limb development.\n\nAuthor SummaryThe EGFR signaling pathway plays a major role in innumerable developmental processes in all animals and its deregulation leads to different types of cancer, as well as many other developmental diseases in humans. Here we explored the integration of inputs from the Wnt- and TGF-beta signaling pathways and the leg-specifying transcription factors Distal-less and Sp1 at enhancer elements of EGFR ligands. These enhancers trigger a specific EGFR-dependent developmental output in the fly leg that is limited to specifying distal-most fates. Our findings suggest that activation of the EGFR pathway during fly leg development occurs through the activation of multiple EGFR ligand enhancers that are active at different positions along the proximo-distal axis. Similar enhancer elements are likely to control EGFR activation in humans as well. Such DNA elements might be hot spots that cause formation of EGFR-dependent tumors if mutations in them occur. Thus, understanding the molecular characteristics of such DNA elements could facilitate the detection and treatment of cancer.

developmental biology↗

bioRxiv2017

Differing strategies used by motor neurons and glia to achieve robust development of an adult neuropil in Drosophila

In both vertebrates and invertebrates, neurons and glia are generated in a stereotyped order from dedicated progenitors called neural stem cells, but the purpose of invariant lineages is not understood. Here we show that three of the stem cells that produce leg motor neurons in Drosophila also generate a specialized subset of glia, the neuropil glia, which wrap and send processes into the neuropil where motor neuron dendrites arborize. The development of the neuropil glia and leg motor neurons is highly coordinated. However, although individual motor neurons have a stereotyped birth order and transcription factor code, both the number and individual morphologies of the glia born from these lineages are highly plastic, even though the final structure they contribute to is highly stereotyped. We suggest that the shared lineages of these two cell types facilitates the assembly of complex neural circuits, and that the two different birth order strategies - hardwired for motor neurons and flexible for glia - are important for robust nervous system development and homeostasis.

neuroscience↗