Alex Pollen
@brainevodevo.bsky.social
Studying specializations and vulnerabilities of human brain development
10/ Thanks to Manuel Lessi for highlighting a preprint of the study prelights.biologists.com/highlights/d...
Dissecting Gene Regulatory Networks Governing Human Cortical Cell Fate - preLights
A deep dive into how transcription factors shape radial glia fate and clonal dynamics
prelights.biologists.com
January 23, 2026 at 1:16 AM
10/ Thanks to Manuel Lessi for highlighting a preprint of the study prelights.biologists.com/highlights/d...
9/ We hope our study will provide a framework for functionally studying how disease and evolution shape human cortical development.
January 23, 2026 at 1:16 AM
9/ We hope our study will provide a framework for functionally studying how disease and evolution shape human cortical development.
8/ Dual repression of ARX and LMO1 partially rescued the ectopic interneuron cellular state.
January 23, 2026 at 1:16 AM
8/ Dual repression of ARX and LMO1 partially rescued the ectopic interneuron cellular state.
7/ We found a postmitotic role for ARX in safeguarding interneuron identity. Without ARX, the cells display “ectopic" subtype identity, characterized by LMO1 upregulation.
January 23, 2026 at 1:16 AM
7/ We found a postmitotic role for ARX in safeguarding interneuron identity. Without ARX, the cells display “ectopic" subtype identity, characterized by LMO1 upregulation.
6/ Multiple transcription factors converge on shared downstream targets - these hub effector genes are often linked to neurodevelopmental and neuropsychiatric disorders, suggesting disorder related genes are more well connected in the TF regulatory networks.
January 23, 2026 at 1:16 AM
6/ Multiple transcription factors converge on shared downstream targets - these hub effector genes are often linked to neurodevelopmental and neuropsychiatric disorders, suggesting disorder related genes are more well connected in the TF regulatory networks.
5/ We also identified NR2E1 and ARX that have opposing roles in regulating the balance of excitatory versus inhibitory neurogenesis. By combining single cell lineage tracing with Perturb-seq, we discovered their roles in balancing RG lineage plasticity and progression.
January 23, 2026 at 1:16 AM
5/ We also identified NR2E1 and ARX that have opposing roles in regulating the balance of excitatory versus inhibitory neurogenesis. By combining single cell lineage tracing with Perturb-seq, we discovered their roles in balancing RG lineage plasticity and progression.
4/ We identified multiple TFs with new roles in cortical neurogenesis, including ZNF219 that represses neural differentiation.
January 23, 2026 at 1:16 AM
4/ We identified multiple TFs with new roles in cortical neurogenesis, including ZNF219 that represses neural differentiation.
3/ We used CRISPRi to repress 44 transcription factors in human radial glia and then measured the consequences on neurogenesis using single cell RNA sequencing.
January 23, 2026 at 1:16 AM
3/ We used CRISPRi to repress 44 transcription factors in human radial glia and then measured the consequences on neurogenesis using single cell RNA sequencing.
2/ Radial glia are multipotent progenitor cells that give rise to most cells in the cortex, including excitatory neurons, oligodendrocytes and astrocytes, as well as olfactory bulb interneurons and a recently characterized population of cortical interneurons.
January 23, 2026 at 1:16 AM
2/ Radial glia are multipotent progenitor cells that give rise to most cells in the cortex, including excitatory neurons, oligodendrocytes and astrocytes, as well as olfactory bulb interneurons and a recently characterized population of cortical interneurons.
This study was supported by NIH funding and an excellent team of collaborators, including @fennak.bsky.social, @mallarinolab.bsky.social, @searslab.bsky.social, Mike DeBerardine, Aunoy Poddar, Miguel Turrero Garcia, and the Paredes, Harwell lab and Berke labs.
November 7, 2025 at 6:06 PM
This study was supported by NIH funding and an excellent team of collaborators, including @fennak.bsky.social, @mallarinolab.bsky.social, @searslab.bsky.social, Mike DeBerardine, Aunoy Poddar, Miguel Turrero Garcia, and the Paredes, Harwell lab and Berke labs.
Collectively, the broad pattern of inhibitory neuron conservation suggests that, on the mammalian timescale, evolution modifies the brain by ‘teaching old cells new tricks’, rather than inventing novel cell types early in development.
November 7, 2025 at 6:06 PM
Collectively, the broad pattern of inhibitory neuron conservation suggests that, on the mammalian timescale, evolution modifies the brain by ‘teaching old cells new tricks’, rather than inventing novel cell types early in development.
Together, we conclude the TAC3 initial class is conserved across placental mammals, but modifies its gene expression and distribution throughout evolution.
November 7, 2025 at 6:06 PM
Together, we conclude the TAC3 initial class is conserved across placental mammals, but modifies its gene expression and distribution throughout evolution.
In adult mouse, we identified a rare subpopulation of Th interneurons which expresses residual Tac2 (TAC3). Using the Allen institute’s Merscope data, we find this rare Tac2-expressing population is spatially restricted to the ventromedial striatum.
November 7, 2025 at 6:06 PM
In adult mouse, we identified a rare subpopulation of Th interneurons which expresses residual Tac2 (TAC3). Using the Allen institute’s Merscope data, we find this rare Tac2-expressing population is spatially restricted to the ventromedial striatum.
Through integrated analysis of adult mouse, marmoset, and human striatal inhibitory neurons, we confirmed the homology of Th interneurons in adult mouse and TAC3 interneurons in the adult primate.
November 7, 2025 at 6:06 PM
Through integrated analysis of adult mouse, marmoset, and human striatal inhibitory neurons, we confirmed the homology of Th interneurons in adult mouse and TAC3 interneurons in the adult primate.
Surprisingly, we find that the population was hiding in plain sight, but disguised by the loss of TAC3 (called Tac2 in mouse) and gain of Th expression, indicating an unappreciated homology between rodent Th and mammalian TAC3 striatal interneurons.
November 7, 2025 at 6:06 PM
Surprisingly, we find that the population was hiding in plain sight, but disguised by the loss of TAC3 (called Tac2 in mouse) and gain of Th expression, indicating an unappreciated homology between rodent Th and mammalian TAC3 striatal interneurons.
Given the conservation of this initial class in Laurasiatherians and marsupials, we next investigate the Glire lineage (rabbit, naked mole rat, rat, mouse), as the population was reported missing in mouse.
November 7, 2025 at 6:06 PM
Given the conservation of this initial class in Laurasiatherians and marsupials, we next investigate the Glire lineage (rabbit, naked mole rat, rat, mouse), as the population was reported missing in mouse.
Although the TAC3 initial class is conserved to marsupials (opossum and sugar glider), we observe turnover of signaling pathway genes across multiple timescales, and an additional migratory destination in Laurasiatherian (pig and ferret) cortex
November 7, 2025 at 6:06 PM
Although the TAC3 initial class is conserved to marsupials (opossum and sugar glider), we observe turnover of signaling pathway genes across multiple timescales, and an additional migratory destination in Laurasiatherian (pig and ferret) cortex
Through integrative analysis, we find that initial classes of inhibitory neurons are conserved across placental mammals. Surprisingly, this conservation includes the MGE-derived TAC3 initial class, which was previously thought to be a primate-specific striatal interneuron population
November 7, 2025 at 6:06 PM
Through integrative analysis, we find that initial classes of inhibitory neurons are conserved across placental mammals. Surprisingly, this conservation includes the MGE-derived TAC3 initial class, which was previously thought to be a primate-specific striatal interneuron population
We begin by performing cross-species analysis of developing initial classes of both striatal and cortical inhibitory neuron populations by integrating single cell sequencing data from 8 mammals, spanning from primates to marsupials.
November 7, 2025 at 6:06 PM
We begin by performing cross-species analysis of developing initial classes of both striatal and cortical inhibitory neuron populations by integrating single cell sequencing data from 8 mammals, spanning from primates to marsupials.