Biology subjects

Abbas, E.

Publications and source records attributed to Abbas, E..

3 recordsLinked to original sources

bioRxiv2024

The Hox Gene, abdominal A controls timely mitotic entry of neural stem cell and their growth during CNS development in Drosophila

Cell size is a critical determinant of its function and physiology. In this study, we investigated the regulation of stem cell size during Drosophila central nervous system (CNS) development and its association with cell fate. We note that neural stem cells (NSCs) in different regions of ventral nerve cord increase their size at different rates. The, thoracic NSCs grow at a faster rate compared to those in the abdominal region. We show that in addition to its role in apoptosis and nervous system remodeling, abdA also plays an instructive role in regulating the rate of NSC size increase and its timely entry into mitosis. Weak expression of abdA in larval abdominal NSCs was sufficient to retard the rate of their size increase and delay their mitotic entry compared to thoracic NSCs. Knockdown of abdA in NSCs enhances their rate of size increase leading to early mitotic entry, while ectopic abdA expression in thoracic NSCs reduces their size and delays their mitotic entry. We show that abdA-mediated NSC size regulation acts downstream of nutrition-induced NSC activation, which fine-tunes the stem cell potential spatiotemporally. This study highlights the instructive role of abdA in regulating various fates of larval NSCs during CNS patterning. Significance statementO_LIUnderstanding the upstream regulation of various aspects of the cell cycle is crucial; however, the influence of cell size on this process remains largely unknown. C_LIO_LIWe found an instructive role for the Hox gene abdominal A in maintaining the small size of neural stem cells (NSCs) and in regulating the time and rate of mitosis. C_LIO_LIThis mechanism is crucial because it helps NSCs generate the necessary number of neurons at an appropriate developmental stage, thereby contributing to proper central nervous system patterning. C_LI

developmental biology↗

bioRxiv2021

IGF1 Receptor Regulates Upward Firing Rate Homeostasis via the Mitochondrial Calcium Uniporter

Regulation of firing rate homeostasis constitutes a fundamental property of central neural circuits. While intracellular Ca2+ has long been hypothesized to be a feedback control signal, the molecular machinery enabling network-wide homeostatic response remains largely unknown. Here we show that deletion of insulin-like growth factor-1 receptor (IGF1R), a well-known regulator of neurodevelopment and ageing, limits firing rate homeostasis in response to inactivity, without altering the baseline firing rate distribution. Disruption of both synaptic and intrinsic homeostatic plasticity contributed to deficient firing rate homeostatic response. At the cellular level, a fraction of IGF1Rs was localized in mitochondria with the mitochondrial calcium uniporter complex (MCUc). IGF1R deletion suppressed spike burst-evoked mitochondrial Ca2+ (mitoCa2+) by weakening mitochondria-to-cytosol Ca2+ coupling. MCUc overexpression in IGF1R-deficient neurons rescued the deficits in spike-to-mitoCa2+ coupling and firing rate homeostasis. Our findings highlight IGF1R as a key regulator of the integrated homeostatic response by tuning mitochondrial temporal filtering. Decline in mitochondrial reliability for burst transfer may drive dysregulation of firing rate homeostasis in ageing and brain disorders associated with aberrant IGF1R / MCUc signaling.

neuroscience↗

bioRxiv2021

H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion by activating TRNP1 expression

Increase in the size of human neocortex, acquired in evolution, accounts for the unique cognitive capacity of humans. This expansion appears to reflect the evolutionarily-enhanced proliferative ability of basal progenitors (BPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, whether or how the epigenome in BPs differs across species is not known. Here, we report that histone H3 acetylation is a key epigenetic regulation in BP amplification and cortical expansion. Through epigenetic profiling of sorted BPs, we show that H3K9 acetylation is low in murine BPs and high in human BPs. Elevated H3K9ac preferentially increases BP proliferation, increasing the size and folding of the normally smooth mouse neocortex. Mechanistically, H3K9ac drives BP amplification by increasing expression of the evolutionarily regulated gene, TRNP1, in the developing cortex. Our findings demonstrate a previously unknown mechanism that controls cortical architecture. One Sentence SummaryH3K9ac promotes basal progenitor amplification, neocortex expansion and gyrification by activating TRNP1 expression in evolution.

developmental biology↗