Biology subjects

Danda, N.

Publications and source records attributed to Danda, N..

4 recordsLinked to original sources

bioRxiv2025

Post-translational Tuning of Human Cortical Progenitor Neuronal Output

The striking expansion of the human neocortex is driven by the ability of radial glial cells (RGCs) to prolong neurogenesis without exhausting their progenitor pool, thereby producing more neurons, particularly in the upper layers. The mechanisms underlying enhanced human neurogenic output remain unresolved. We hypothesized that post-translational modification of conserved proteins could provide a flexible mechanism supporting species-specific patterns of neurogenesis. Here, we identify phosphorylation of the proneural factor NEUROGENIN2 as a regulator of human RGC neuronal output by modulating its pioneering-like activity, at the expense of its transactivation function. This, in turn, remodels the RGC chromatin landscape, resulting in a forward temporal shift of RGC gene regulatory networks and leading to increased neuronal production biased towards upper-layer neurons. Our work proposes a conceptual framework for how subtle modifications of conserved processes, and not just new genes, encode tunable mechanisms for species-specific trajectories of brain development.

developmental biology↗

bioRxiv2023

Developmental transcriptional control of mitochondrial homeostasis is required for activity-dependent synaptic connectivity

During neuronal circuit formation, local control of axonal organelles ensures proper synaptic connectivity. Whether this process is genetically encoded is unclear and if so, its developmental regulatory mechanisms remain to be identified. We hypothesized that developmental transcription factors regulate critical parameters of organelle homeostasis that contribute to circuit wiring. We combined cell type-specific transcriptomics with a genetic screen to discover such factors. We identified Telomeric Zinc finger-Associated Protein (TZAP) as a temporal developmental regulator of neuronal mitochondrial homeostasis genes, including Pink1. In Drosophila, loss of dTzap function during visual circuit development leads to loss of activity-dependent synaptic connectivity, that can be rescued by Pink1 expression. At the cellular level, loss of dTzap/TZAP leads to defects in mitochondrial morphology, attenuated calcium uptake and reduced synaptic vesicle release in fly and mammalian neurons. Our findings highlight developmental transcriptional regulation of mitochondrial homeostasis as a key factor in activity-dependent synaptic connectivity.

neuroscience↗

bioRxiv2021

The Amyloid Precursor Protein regulates human cortical neurogenesis

The approximately 16 billion neurons of the human neocortex are derived from a relatively limited number of developmental neural stem cells (NSCs). During embryogenesis, human cortical NSCs initially generate neurons at a particularly slow rate while preserving their progenitor state for a relatively long time. How this balance between the progenitor state and neurogenic state is regulated, and whether it contributes to species-specific brain patterning, is poorly understood. Here we show that the characteristic potential of human NSCs to remain in a progenitor state as they generate neurons for a prolonged amount of time requires the Amyloid Precursor Protein (APP). In contrast, APP is dispensable in mouse NSCs, which undergo neurogenesis at a much faster rate. Mechanistically, loss of APP cell-autonomously accelerates neurogenesis through activation of the AP1 transcription factor and repression of WNT signaling. We propose that the fine balance between self-renewal and differentiation is homeostatically regulated by APP, which may contribute to human-specific temporal patterns of neurogenesis.

developmental biology↗

bioRxiv2019

Single-cell resolution view of the transcriptional landscape of developing Drosophila eye.

Faithful and reliable quantification of gene expression at a single-cell level is an outstanding challenge in developmental biology. Most existing approaches face a trade-off between the signal to noise ratio, resolution, and sensitivity. Here, we present a novel approach for in situ quantification of gene expression in a developing tissue. Our pipeline combines computational prediction of transcription factor targets, gene tagging, fluorescent reporter imaging, state-of-the-art image analysis, and automated cell-type identification. By applying this approach to identify the sequence of quantitative changes in gene expression which govern the development of the Drosophila neural retina, we demonstrate the feasibility of our method. We analyze the targets of Atonal (Ato), a transcription factor that controls the transition from eye disc progenitor cell to photoreceptor neurons. We utilized recombineering and genomic engineering to tag all predicted Ato targets with novel transcriptional reporters. These reporters enable following the expression of both regulator and regulated genes to accurately quantify their expression levels in individual cells. Our complete computational pipeline identifies nuclei in the eye discs and detects different states of cells as they progress through differentiation. Based on detailed gene expression analysis, our technique revealed genes likely to be direct Ato targets and provided insight into how gene expression changes drive the specification of photoreceptors.

developmental biology↗