An RNAi screen for secreted factors and cell-surface players in coordinating neuron and glia development in Drosophila

Abstract

The establishment of the functional nervous system requires coordinated development of neurons and glia in the embryo. Our understanding of underlying molecular and cellular mechanisms, however, remains limited. The developing Drosophila visual system is an excellent model for understanding the developmental control of the nervous system. By performing a systematic transgenic RNAi screen, we investigated the requirements of secreted proteins and cell-surface receptors for the development of photoreceptor neurons (R cells) and wrapping glia (WG) in the Drosophila visual system. From the screen, we identified seven genes whose knockdown disrupted the development of R cells and/or WG, including amalgam (ama), domeless (dome), epidermal growth factor receptor (EGFR), kuzbanian (kuz), N-Cadherin (CadN), neuroglian (nrg), and shotgun (shg). Cell-type-specific analysis revealed that ama is required in the developing eye disc for promoting cell proliferation and differentiation, which is essential for the migration of glia in the optic stalk. Our results also suggest that nrg functions in both eye disc and WG for coordinating R-cell and WG development.

Animal Models of Depression: What Can They Teach Us about the Human Disease?

“…The use of Cre-driver mouse lines for targeting local specific brain areas associated with depression and emotionality such as forebrain, hippocampus and VTA, provides a new approach to investigate proof of concept as to how the brain modulates mood and mood disorders [ 311 , 312 ]. Within the development of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9) system (CRISPR/Cas9) technology, the new generation of KO mice were developed in order to investigate the role of specific proteins on depression-like phenotype development and for further translation to clinical depression [ 313 , 314 , 315 ].…”

Human Astrocytes Model Derived from Induced Pluripotent Stem Cells

“…Astrocytes also regulate neuronal synapses by promoting synaptogenesis [ 11 ] or by modulating synaptic transmission through the transport of various amino acids, such as glutamate [ 12 , 13 ]. While previous reports have relied mainly on transcriptome and protein expression analyses [ 14 ] or calcium imaging studies [ 15 , 16 ] to characterize iPSC-astrocytes derived lines, only a few groups have performed co-culture with neurons [ 17 , 18 ] or investigated their glucose metabolism [ 19 , 20 ] and to the best of our knowledge, none has conducted all these analyses concurrently.…”

The Effect of Lead Exposure on Autism Development

“…Prior research has emphasized the role of proper molecular structure in the adequate functioning of neurological mechanisms [ 36 ]. Indeed, several neuropsychiatric illnesses are associated with inconsistencies of molecular pathways, specifically, alterations within neurons and synapses [ 37 ]. Autistic individuals have been shown to possess a variety of dysfunctionalities within their dopaminergic, cholinergic, and glutamatergic systems [ 37 ].…”

“…Indeed, several neuropsychiatric illnesses are associated with inconsistencies of molecular pathways, specifically, alterations within neurons and synapses [ 37 ]. Autistic individuals have been shown to possess a variety of dysfunctionalities within their dopaminergic, cholinergic, and glutamatergic systems [ 37 ]. Along with several other neurological dysfunctions, abnormal levels of dopamine transporters have been noted in autistic individuals [ 37 ].…”

“…Autistic individuals have been shown to possess a variety of dysfunctionalities within their dopaminergic, cholinergic, and glutamatergic systems [ 37 ]. Along with several other neurological dysfunctions, abnormal levels of dopamine transporters have been noted in autistic individuals [ 37 ]. In addition to the deterioration within the dopaminergic system, autistic individuals have been shown to possess restricted interests and decrements in energy metabolism associated with changes in the cholinergic system [ 38 ].…”