A5045420315- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Wnt/β-catenin signaling in development and cancer
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- Mosquito-borne diseases and control
- COVID-19 Impact on Reproduction
- Ion channel regulation and function
- Cancer-related molecular mechanisms research
- Genetics, Aging, and Longevity in Model Organisms
- Congenital heart defects research
- Attention Deficit Hyperactivity Disorder
- MicroRNA in disease regulation
- RNA regulation and disease
- Virology and Viral Diseases
- Berberine and alkaloids research
- Neuroethics, Human Enhancement, Biomedical Innovations
- Zebrafish Biomedical Research Applications
- RNA modifications and cancer
- Global Maternal and Child Health
University of California, San Francisco
2016-2025
Broad Center
2016-2025
Neurological Surgery
2020-2025
Broad Institute
2025
University of California, Los Angeles
2020
The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces range mild to severe pathologies, including microcephaly. To understand the pathophysiology infection, we used models developing that faithfully recapitulate tissue architecture in early midgestation. We identify cell populations are most susceptible primary human tissue, provide evidence for mechanism viral entry, show commonly...
Neuronal subtype generation in the mammalian central nervous system is governed by competing genetic programs. The medial ganglionic eminence (MGE) produces two major cortical interneuron (IN) populations, somatostatin (Sst) and parvalbumin (Pvalb), which develop on different timelines. extent to external signals influence these identities remains unclear. Pvalb-positive INs are crucial for circuit regulation but challenging model vitro. We grafted mouse MGE progenitors into diverse 2D 3D...
Cortical function critically depends on inhibitory/excitatory balance. inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers adjusted by programmed cell death. Here, we show that loss of clustered gamma protocadherins (Pcdhg), but not genes alpha or beta clusters, increased dramatically cIN BAX-dependent death mice. Surprisingly, electrophysiological morphological properties Pcdhg-deficient wild-type cINs during period were...
Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex where they make connections with locally produced excitatory glutamatergic neurons. function critically depends on number of cINs, which is also key to establishing appropriate inhibitory/excitatory balance. The final cINs determined during a postnatal period programmed cell death (PCD) when ~40% young eliminated. Previous work shows that loss clustered gamma protocadherins (Pcdhgs), but not...
The generation of neuronal subtypes in the mammalian central nervous system is driven by competing genetic programs. medial ganglionic eminence (MGE) gives rise to two major cortical interneuron (cIN) populations, marked Somatostatin (Sst) and Parvalbumin (Pvalb), which develop on different timelines. extent external signals influence these identities remains poorly understood. Pvalb-positive cINs are particularly important for regulating circuits through strong perisomatic inhibition, yet...
The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces range mild to severe pathologies, including placental damage microcephaly. However, the placenta’s role in viral transmission mechanisms microcephaly have not been addressed primary human tissues. Moreover, there is an urgent need for drugs that can prevent developmental defects following infection. Here, we identify cell...
ABSTRACT Astrocyte specification during development is influenced by both intrinsic and extrinsic factors, but the precise contribution of each remains poorly understood. Here we show that septal astrocytes from Nkx2.1 Zic4 expressing progenitor zones are allocated into non-overlapping domains medial (MS) lateral nuclei (LS) respectively. Astrocytes in these areas exhibit distinctive molecular morphological features tailored to unique cellular synaptic circuit environment nucleus. Using...
Neurogenesis and gliogenesis continue in the Ventricular-Subventricular Zone (V-SVZ) of adult rodent brain. B1 cells are astroglial derived from radial glia that function as primary progenitors or neural stem (NSCs) V-SVZ. cells, which have a small apical contact with ventricle, decline numbers during early postnatal life, yet neurogenesis continues into adulthood. Here we found second population V-SVZ (B2 cells), do not NSCs B2 cell increase postnatally, remain constant 12-month-old mice...
Summary Nuclear compartments play diverse roles in regulating gene expression, yet the molecular forces and components driving compartment formation are not well understood. Studying how lncRNA Xist establishes inactive-X-chromosome (Xi)-compartment, we found that RNA-binding-proteins PTBP1, MATR3, TDP43, CELF1 form a condensate to create an Xi-domain can be sustained absence of . The E-repeat-sequence serves multivalent binding-platform for these proteins. Without E-repeat, initially coats...
Abstract Cortical interneurons are indispensable for proper function of neocortical circuits. Changes in interneuron development and implicated human disorders, such as autism spectrum disorder epilepsy. In order to understand human-specific features cortical well the origins neurodevelopmental disorders it is crucial identify molecular programs underlying subtype specification. Recent studies have explored gene expression mouse specification maturation. We applied single-cell RNA sequencing...
Cortical function critically depends on inhibitory/excitatory balance. inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers adjusted by programmed cell death. Previously, we showed that loss of clustered gamma protocadherins (
Abstract Cortical function critically depends on inhibitory/excitatory balance. GABAergic cortical inhibitory interneurons (cINs) are born in the ventral forebrain. After completing their migration into cortex, final numbers adjusted-during a period of postnatal development - by programmed cell death (PCD). The mechanisms that regulate cIN elimination remain controversial. Here we show genes protocadherin (Pcdh)-γ gene cluster, but not Pcdh-α or Pcdh-β clusters, required for survival cINs...