Biology subjects

Lele, Z.

Publications and source records attributed to Lele, Z..

3 recordsLinked to original sources

bioRxiv2021

Somatic junctions connect microglia and developing neurons

Microglia are the resident immune cells of the brain with multiple homeostatic and regulatory roles. Emerging evidence also highlights the fundamental transformative role of microglia in brain development. While tightly controlled, bi-directional communication between microglia and neuronal progenitors or immature neurons has been postulated, the main sites of interaction and the underlying mechanisms remain elusive. By using correlated light and electron microscopy together with super-resolution imaging, here we provide evidence that microglial processes form specialized nanoscale contacts with the cell bodies of developing and immature neurons throughout embryonic, early postnatal and adult neurogenesis. These early developmental contacts are highly reminiscent to somatic purinergic junctions that are instrumental for microglia-neuron communication in the adult brain. We propose that early developmental formation of somatic purinergic junctions represents an ideal interface for microglia to monitor the status of developing neurons and to direct prenatal, early postnatal and adult neurogenesis.

neuroscience↗

bioRxiv2019

ABHD4-dependent developmental anoikis protects the prenatal brain from pathological insults

In light of the astronomical number of cell divisions taking place in restricted neurogenic niches, brain malformations caused by ectopic proliferation of misplaced progenitor cells are surprisingly rare. Here, we show that a process we term developmental anoikis distinguishes the abnormal detachment of progenitor cells from the normal delamination of daughter neuroblasts in the developing mouse neocortex. By using in vivo gain-of-function, loss-of-function, and rescue manipulations together with correlated confocal and super-resolution imaging, we identify the endocannabinoid-metabolizing enzyme abhydrolase domain containing 4 (ABHD4) as an essential mediator for the elimination of abnormally detached cells. Consequently, rapid ABHD4 downregulation is necessary for delaminated daughter neuroblasts to escape from anoikis. Moreover, ABHD4 is required for fetal alcohol-induced apoptosis, but not for the well-established form of developmentally controlled programmed cell death. These results suggest that ABHD4-mediated developmental anoikis specifically protects the embryonic brain from the consequences of sporadic delamination errors and teratogenic insults.

developmental biology↗

bioRxiv2019

Microglia monitor and protect neuronal function via specialized somatic purinergic junctions

Microglia are the main immune cells in the brain with emerging roles in brain homeostasis and neurological diseases, while mechanisms underlying microglia-neuron communication remain elusive. Here, we identify a novel site of interaction between neuronal cell bodies and microglial processes in mouse and human brain. Somatic microglia-neuron junctions possess specialized nanoarchitecture optimized for purinergic signaling. Activity of neuronal mitochondria is linked with microglial junction formation, which is rapidly induced in response to neuronal activation and blocked by inhibition of P2Y12-receptors (P2Y12R). Brain injury-induced changes at somatic junctions trigger P2Y12R-dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Collectively, our results suggest that microglial processes at these junctions are in ideal position to monitor and protect neuronal functions in both the healthy and injured brain.\n\nOne-sentence summaryNeuronal cell bodies possess specialized, pre-formed sites, through which microglia monitor their status and exert neuroprotection.

neuroscience↗