Biology subjects

Mikalauskaite, D.

Publications and source records attributed to Mikalauskaite, D..

3 recordsLinked to original sources

bioRxiv2025

Regulation of Hippo signaling by Atrophin in the developing Drosophila wing

Organ development is directed through integration of signaling networks and their transcriptional programs. We have investigated connections between Hippo signaling and the transcriptional co-repressor Atrophin. We find that Atrophin modulates Hippo signaling outputs in the developing Drosophila wing and does so in distinct ways in different regions. Near the dorsal-ventral boundary, loss of Atrophin leads to upregulation of targets of the Hippo pathway transcription factor Yorkie. This is explained by impairment of Notch signaling, and consequent downregulation of Vestigial, which normally competes with Yorkie for binding to Scalloped. In proximal regions of the wing disc, loss of Atrophin leads to downregulation of Yorkie activity. This is explained by downregulation of Dachs, as Dachs inhibits Warts, the central kinase controlling Yorkie activity. Downregulation of Dachs is explained by modulation of its upstream regulators Dachsous and Four-jointed, which is explained in turn by our discovery that Atrophin interacts genetically and physically with Vestigial and competes with Scalloped for Vestigial binding. These studies define new roles for Atrophin and enhance our understanding of the interplay of transcriptional activators and repressors that modulate Hippo signaling to shape wing development.

developmental biology↗

bioRxiv2020

Cellular expression and functional roles of all 26 neurotransmitter GPCRs in the C. elegans egg-laying circuit

Maps of the synapses made and neurotransmitters released by all neurons in model systems such as C. elegans have left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit of C. elegans as a model, we mapped which cells express each of the 26 neurotransmitter G protein coupled receptors (GPCRs) of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. The egg-laying circuit appears to use redundancy and compensation to achieve functional robustness, as receptor knockouts reveal few defects; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits.

neuroscience↗

bioRxiv2019

The evolutionary origins and diversity of the neuromuscular system of paired appendages in batoids

Appendage patterning and evolution have been active areas of inquiry for the past two centuries. While most work has centered on the skeleton, particularly that of amniotes, the evolutionary origins and molecular underpinnings of the neuromuscular diversity of fish appendages have remained enigmatic. The fundamental pattern of segmentation in amniotes, for example, is that all muscle precursors and spinal nerves enter either the paired appendages or body wall at the same spinal level. The condition in finned vertebrates is not understood. To address this gap in knowledge, we investigated the development of muscles and nerves in unpaired and paired fins of skates and compared them to those of chain catsharks. During skate and shark embryogenesis, cell populations of muscle precursors and associated spinal nerves at the same axial level contribute to both appendages and body wall, perhaps representing an ancestral condition of gnathostome appendicular neuromuscular systems. Remarkably in skates, this neuromuscular bifurcation as well as colinear Hox expression extend posteriorly to pattern a broad paired fin domain. In addition, we identified migratory muscle precursors (MMPs), which are known to develop into paired appendage muscles with Pax3 and Lbx1 gene expression, in the dorsal fins of skates. Our results suggest that muscles of paired fins have evolved via redeployment of the genetic program of MMPs that were already involved in dorsal fin development. Appendicular neuromuscular systems most likely have emerged as side branches of body wall neuromusculature and have been modified to adapt to distinct aquatic and terrestrial habitats.

evolutionary biology↗