scholarly journals nalyot, a Mutation of the Drosophila Myb-Related Adf1 Transcription Factor, Disrupts Synapse Formation and Olfactory Memory

Neuron ◽  
2000 ◽  
Vol 27 (1) ◽  
pp. 145-158 ◽  
Author(s):  
James DeZazzo ◽  
David Sandstrom ◽  
Steve de Belle ◽  
Klara Velinzon ◽  
Patrick Smith ◽  
...  
2020 ◽  
Vol 295 (39) ◽  
pp. 13677-13690
Author(s):  
Jeong Su Byun ◽  
Mihee Oh ◽  
Seonha Lee ◽  
Jung-Eun Gil ◽  
Yeajin Mo ◽  
...  

Astrocytes perform multiple essential functions in the developing and mature brain, including regulation of synapse formation, control of neurotransmitter release and uptake, and maintenance of extracellular ion balance. As a result, astrocytes have been implicated in the progression of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. Despite these critical functions, the study of human astrocytes can be difficult because standard differentiation protocols are time-consuming and technically challenging, but a differentiation protocol recently developed in our laboratory enables the efficient derivation of astrocytes from human embryonic stem cells. We used this protocol along with microarrays, luciferase assays, electrophoretic mobility shift assays, and ChIP assays to explore the genes involved in astrocyte differentiation. We demonstrate that paired-like homeodomain transcription factor 1 (PITX1) is critical for astrocyte differentiation. PITX1 overexpression induced early differentiation of astrocytes, and its knockdown blocked astrocyte differentiation. PITX1 overexpression also increased and PITX1 knockdown decreased expression of sex-determining region Y box 9 (SOX9), known initiator of gliogenesis, during early astrocyte differentiation. Moreover, we determined that PITX1 activates the SOX9 promoter through a unique binding motif. Taken together, these findings indicate that PITX1 drives astrocyte differentiation by sustaining activation of the SOX9 promoter.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 415
Author(s):  
Terezija Miškić ◽  
Ivica Kostović ◽  
Mladen-Roko Rašin ◽  
Željka Krsnik

Cut-Like Homeobox 2 (Cux2) is a transcription factor involved in dendrite and spine development, and synapse formation of projection neurons placed in mouse upper neocortical layers. Therefore, Cux2 is often used as an upper layer marker in the mouse brain. However, expression of its orthologue CUX2 remains unexplored in the human fetal neocortex. Here, we show that CUX2 protein is expressed in transient compartments of developing neocortical anlage during the main fetal phases of neocortical laminar development in human brain. During the early fetal phase when neurons of the upper cortical layers are still radially migrating to reach their final place in the cortical anlage, CUX2 was expressed in the marginal zone (MZ), deep cortical plate, and pre-subplate. During midgestation, CUX2 was still expressed in the migrating upper cortical neurons as well as in the subplate (SP) and MZ neurons. At the term age, CUX2 was expressed in the gyral white matter along with its expected expression in the upper layer neurons. In sum, CUX2 was expressed in migratory neurons of prospective superficial layers and in the diverse subpopulation of transient postmigratory SP and MZ neurons. Therefore, our findings indicate that CUX2 is a novel marker of distinct transient, but critical histogenetic events during corticogenesis. Given the Cux2 functions reported in animal models, our data further suggest that the expression of CUX2 in postmigratory SP and MZ neurons is associated with their unique dendritic and synaptogenesis characteristics.


2020 ◽  
Author(s):  
Yeoh Sue Lynn ◽  
Alina Letzel ◽  
Clemence Bernard Hannah Somerfield ◽  
Kyle Kyser ◽  
Emily Lin ◽  
...  

AbstractThe transcription factor Odd-skipped has been implicated in many developmental processes in Drosophila melanogaster. Odd-skipped is expressed in a small cluster of neurons (Slater, Levy et al.) in the developing and adult CNS but its role in neurogenesis has so far not been addressed. Here we show that Odd-skipped plays a pivotal role in neurite growth and arborization during development. Loss-of-Odd-skipped function prevents neurite outgrowth whereas over and miss-expression causes neurite growth and arborization defects. In addition, miss-expression of Odd-skipped can induce cell death in some neural sub types. The neurite growth and arborization defects associated with Odd-skipped over expression correlates with a reduction in the pre-synaptically targeted protein Bruchpilot in axonal arbours suggesting an overall decrease in Odd neural synapse formation. This is supported by behavioural data showing that larvae in which Odd-skipped is overexpressed behave similarly to larvae in which Odd neurons are silenced showing that increasing Odd-skipped protein levels affect neural function. Finally, we demonstrate that using RNAi against Odd-skipped does not knock down Odd-skipped protein but instead cause an increase in protein levels compared to control larvae. This data demonstrates that RNAi can cause up-regulation of protein levels highlighting the importance of verifying protein levels when using RNAi approaches for knock-down.


2019 ◽  
Author(s):  
Julia L. Meng ◽  
Zarion D. Marshall ◽  
Meike Lobb-Rabe ◽  
Ellie S. Heckscher

Abstract:In many CNS regions, neuronal birth timing is associated with circuit membership. In Drosophila larvae, we show U motor neurons are a temporal cohort—a set of non-identical, contiguously-born neurons from a single neuronal stem cell that contribute to the same circuit. We prolong expression of a temporal transcription factor, Hunchback, to increase the number of U motor neurons with early-born molecular identities. On the circuit level, this expands and re-wires the U motor neuron temporal cohort. On the cell biological level, we find novel roles for Hunchback in motor neuron target selection, neuromuscular synapse formation, dendrite morphogenesis, and behavior. These data provide insight into the relationship between stem cell and circuit, show that Hunchback is a potent regulator of circuit assembly, and suggest that temporal transcription factors are molecules that could be altered during evolution or biomedical intervention for the generation of novel circuits.


2021 ◽  
Vol 118 (13) ◽  
pp. e2025530118
Author(s):  
Ivan J. Santiago ◽  
Dawei Zhang ◽  
Arunesh Saras ◽  
Nicholas Pontillo ◽  
Chundi Xu ◽  
...  

The layered compartmentalization of synaptic connections, a common feature of nervous systems, underlies proper connectivity between neurons and enables parallel processing of neural information. However, the stepwise development of layered neuronal connections is not well understood. The medulla neuropil of the Drosophila visual system, which comprises 10 discrete layers (M1 to M10), where neural computations underlying distinct visual features are processed, serves as a model system for understanding layered synaptic connectivity. The first step in establishing layer-specific connectivity in the outer medulla (M1 to M6) is the innervation by lamina (L) neurons of one of two broad, primordial domains that will subsequently expand and transform into discrete layers. We previously found that the transcription factor dFezf cell-autonomously directs L3 lamina neurons to their proper primordial broad domain before they form synapses within the developing M3 layer. Here, we show that dFezf controls L3 broad domain selection through temporally precise transcriptional repression of the transcription factor slp1 (sloppy paired 1). In wild-type L3 neurons, slp1 is transiently expressed at a low level during broad domain selection. When dFezf is deleted, slp1 expression is up-regulated, and ablation of slp1 fully rescues the defect of broad domain selection in dFezf-null L3 neurons. Although the early, transient expression of slp1 is expendable for broad domain selection, it is surprisingly necessary for the subsequent L3 innervation of the M3 layer. DFezf thus functions as a transcriptional repressor to coordinate the temporal dynamics of a transcriptional cascade that orchestrates sequential steps of layer-specific synapse formation.


2020 ◽  
Author(s):  
Hajime Shiotani ◽  
Muneaki Miyata ◽  
Takeshi Kameyama ◽  
Kenji Mandai ◽  
Miwako Yamasaki ◽  
...  

Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.


Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A92-A92
Author(s):  
Takazoe K ◽  
Foti R ◽  
Hurst La ◽  
Atkins Rc ◽  
Nikolic‐Paterson DJ.

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