The Life Sciences Departments in Harvard Faculty of Arts and Sciences seek to recruit a tenure-track professor whose research is at the interface of AI and life sciences, from methodological developme...

The cerebral cortex drives human cognition through the coordinated activity of discrete cortical areas, each harboring specialized molecular, structural and functional characteristics. Central to this organization is the prefrontal cortex (PFC), a hub for executive function that displays disproportionate expansion in humans and selective vulnerability to neurodevelopmental disorders. Previous work has identified a collection of PFC-enriched marker genes with dynamic expression trajectories, and re-analysis of these datasets converge these markers into 18 distinct molecular signatures of spatiotemporal PFC identity. However, the intrinsic gene networks that coordinate these molecular signatures to shape the human PFC remains unclear. Through pooled CRISPR activation screens in human primary cortical tissues, we have evaluated the ability of PFC-enriched transcription factors to intrinsically pattern PFC molecular identity. Our screens identify novel roles for the neurogenesis regulator, YBX1, in the activation of human PFC fate. In parallel screens and knock-down experiments in human cortical organoids, we define how YBX1 acts in concert with other PFC determinants to activate molecular signatures of PFC identity. Our findings support a model in which PFC patterning is orchestrated by cohorts of intrinsic determinants that initiate, potentiate, and modulate PFC gene signatures, conferring robustness to the development of the human PFC. ### Competing Interest Statement The authors have declared no competing interest. NIH, R00NS111731, R01MH132689, UM1MH130991, RF1MH132662, U24HG002371 Brain & Behavior Research Foundation, https://ror.org/03a63f080, Young Investigator Award Alfred P. Sloan Foundation, https://ror.org/052csg198, Sloan Fellowship Rose Hills Foundation, Innovation Award Esther A. & Joseph Klingenstein Fund, Klingenstein-Simons Fellowship Simons Foundation, https://ror.org/01cmst727, Klingenstein-Simons Fellowship Ablon Trust, Ablon Scholar Award Department of Biological Chemistry, UCLA Zamenhof Scholarship UCLA Eli and Edythe Broad Center of Regenerative Medicine, Innovation Award, Stem Cell Research Training Program University of California, Los Angeles, https://ror.org/046rm7j60, Eugene V. Cota-Robles Award California Institute for Regenerative Medicine, https://ror.org/033m8b439, DISC0-14514, DISC4-16337 National Science Foundation, Graduate Research Fellowship Program

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During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this co...

Nature - Genetic manipulation of blastoids reveals the role of recently emerged transposable elements and genes in human development.

The human pelvis exhibits distinct spatiotemporal ossification patterns and an ilium cartilage growth plate that is shifted perpendicularly compared with those of other mammals and non-human primates—...

The Thawani Lab at Columbia University describing their research on mobile genome, cryo-electron microscopy and genome engineering

HARE5, a human accelerated region enhancer, modulates cortical development by influencing neural progenitor cell behaviour, leading to an enlarged neocortex with increased functional independence betw...

After birth, sensory inputs to neurons trigger the induction of activity-dependent genes (ADGs) that mediate many aspects of neuronal maturation and plasticity. To identify human-specific ADGs, we cha...

A major challenge in human evolutionary biology is to pinpoint genetic differences that underlie human-specific traits, such as increased neuron number and differences in cognitive behaviors. We used human-chimpanzee tetraploid cells to distinguish gene expression changes due to cis -acting sequence variants that change local gene regulation, from trans expression changes due to species differences in the cellular environment. In neural progenitor cells, examination of both cis and trans changes – combined with CRISPR inhibition and transcription factor motif analyses – identified cis -acting, species-specific gene regulatory changes, including to TNIK , FOSL2 , and MAZ , with widespread trans effects on neurogenesis-related gene programs. In excitatory neurons, we identified POU3F2 as a key cis -regulated gene with trans effects on synaptic gene expression and neuronal firing. This study identifies cis -acting genomic changes that cause cascading trans gene regulatory effects to contribute to human neural specializations, and provides a general framework for discovering genetic differences underlying human traits. ### Competing Interest Statement C.A.W. is on the SAB of Bioskyrb Genomics (cash, equity) and Mosaica Therapeutics (cash, equity), and is an advisor to Maze Therapeutics (equity), but these have no relevance to this work. The remaining authors declare no competing interests.

Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD) are common neurodegenerative disorders for which the mechanisms driving neuronal death remain unclear. ...

The long-term success of introduced populations depends on both their initial size and ability to compete against existing residents, but it remain...