Biology subjects

Nagarkar-Jaiswal, S.

Publications and source records attributed to Nagarkar-Jaiswal, S..

3 recordsLinked to original sources

bioRxiv2024

Inseparable/IER3IP1 are essential for cytokinesis in Drosophila neuroblast and human cells

To unveil the molecular players that maintain neural stem cell homeostasis, we conducted a genetic screen in Drosophila and isolated an uncharacterized gene that we named Inseparable (Insep). Insep is the Drosophila homologue of human IER3IP1, a gene associated with Microcephaly, Epilepsy, and Neonatal Diabetes Syndrome (MEDS-1). We show that Insep loss leads to early larval lethality with small brains and these phenotypes can be rescued by expressing IER3IP1 indicating that their biological function is conserved through evolution. The Insep deficient neuroblasts fail to complete cytokinesis and show excessive accumulation of Rab11 vesicles in the cytoplasm. Similarly, IER3IP1 depletion in human cells leads to cytokinesis failure and accumulation of Rab11 vesicles. Insep and IER3IP1 localize to Rab11 vesicles and interact with Rab11. The pathogenic mutations in IER3IP1 perturb its localization to Rab11 vesicles and interaction with Rab11. These results suggest that Insep and IER3IP1 work along with Rab11 and may regulate fusion of Rab11 vesicles to the advancing furrow during cytokinesis.

cell biology↗

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

Transsynaptic interactions between IgSF proteins DIP-α and Dpr10 are required for motor neuron targeting specificity in Drosophila

The Drosophila larval neuromuscular system provides an ideal context in which to study synaptic partner choice, because it contains a small number of pre- and postsynaptic cells connected in an invariant pattern. The discovery of interactions between two subfamilies of IgSF cell surface proteins, the Dprs and the DIPs, provided new candidates for cellular labels controlling synaptic specificity. Here we show that DIP- is expressed by two identified motor neurons, while its binding partner Dpr10 is expressed by postsynaptic muscle targets. Removal of either DIP- or Dpr10 results in loss of specific axonal branches and NMJs formed by one motor neuron, MNISN-1s, while other branches of the MNISN-1s axon develop normally. The temporal and spatial expression pattern of dpr10 correlates with muscle innervation by MNISN-1s during embryonic development. We propose a model whereby DIP- and Dpr10 on opposing synaptic partners interact with each other to generate proper motor neuron connectivity.

neuroscience↗