Biology subjects

Figueroa Velez, D. X.

Publications and source records attributed to Figueroa Velez, D. X..

3 recordsLinked to original sources

bioRxiv2025

Fluid-Niche and Microglial Signatures Prime Robust Intraventricular Macrophage Response to Blood During Brain Development

Intraventricular macrophages (IVMs) reside in cerebrospinal fluid (CSF) and are considered a border-associated macrophage (BAM) population in the brain. Although they represent the first line of defense against intraventricular challenges, their developmental roles and responses to injury are poorly understood. This knowledge is relevant for conditions including neonatal intraventricular hemorrhage (IVH), where blood extravasates into brain ventricles, leading to life-long negative sequelae including cerebral palsy and hydrocephalus. Here, we show that IVMs are first responders to blood in developing brain ventricles, phagocytosing red blood cells and upregulating iron-processing machinery. Live imaging of developing mouse ventricles and choroid plexus revealed that IVMs are dynamic and morphologically distinct from non-IVM macrophages. Their transcriptional profiles distinguish them from other BAMs as they also exhibit signatures of "youth-associated microglia" and characteristics of cavity macrophages found in fluid niches such as the peritoneum. Our findings provide insights into IVM development and function, highlighting their therapeutic potential.

developmental biology↗

bioRxiv2021

Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave

Microglia, the brains resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using sustained colony-stimulating factor 1 receptor inhibition, we report an unprecedented level of microglial depletion and establish a model system that achieves an empty microglial niche in the adult brain. We identify a myeloid cell that migrates from an important neurogenic niche, the subventricular zone, and associated white matter areas. These cells exhibit tremendous chemotaxis potential, migrating radially and tangentially in a dynamic wave and filling the brain in a distinct pattern, to fully replace the microglial-depleted brain. These repopulating cells are enriched in disease-associated microglia genes and exhibit distinct phenotypic and functional profiles to endogenous microglia. Our findings shed light on the overlapping and distinct functional complexity and diversity of myeloid cells of the CNS and provide new insight into myeloid cell dynamics in an empty microglial niche without contributions from bone marrow-derived cells.

immunology↗

bioRxiv2018

Early Visual Experience Shapes Binocularity in the Mouse Thalamocortical Pathway

Monocular deprivation (MD) during the juvenile critical period leads to long-lasting impairments in binocular function and visual acuity. The site of these changes has been widely considered to be cortical. However, recent evidence indicates that binocular integration may first occur in the dorsolateral geniculate nucleus of the thalamus (dLGN), raising the question of whether MD during the critical period may produce long-lasting deficits in dLGN binocular integration. Using in vivo two-photon Ca2+ imaging of dLGN afferents and excitatory neurons in superficial layers of primary visual cortex (V1), we demonstrate that critical-period MD leads to a persistent and selective loss of binocular dLGN inputs, while leaving spatial acuity in the thalamocortical pathway intact. Despite being few in number, binocular dLGN boutons display remarkably robust visual responses, on average twice stronger than monocular boutons, and their responses are exquisitely well-matched between the eyes. To our surprise, we found that MD leads to a profound binocular mismatch of response amplitude, spatial frequency and orientation tuning detected at the level of single thalamocortical synapses. In comparison, V1 neurons display deficits in both binocular integration and spatial acuity following MD. Our data provide the most compelling evidence to date demonstrating that following critical-period MD, binocular deficits observed at the level of V1 may at least in part originate from dLGN binocular dysfunction, while spatial acuity deficits arise from cortical circuits. These findings highlight a hitherto unknown role of the thalamus as a site for developmental refinement of binocular vision.

neuroscience↗