Biology subjects

Noguchi, H.

Publications and source records attributed to Noguchi, H..

18 recordsLinked to original sources

bioRxiv2026

m1A58 governs two steps of human initiator-methionine tRNA metabolism: maturation and XRN2-mediated decay

N{superscript 1}-methyladenosine at position 58 (m{superscript 1}A58), installed by the TRMT6/TRMT61A complex, is a highly conserved structural modification implicated in tRNA stability and human disease. In yeast, loss of m{superscript 1}A58 disrupts initiator methionine tRNA (tRNA) metabolism through defects in precursor processing and rapid tRNA decay, but whether these mechanisms operate in human cells has remained unclear. Here, using acute degron-mediated depletion of TRMT6 in human HCT116 cells combined with precursor-resolved tRNA sequencing, we show that m{superscript 1}A58 controls two distinct steps of tRNA metabolism. TRMT6 depletion selectively reduces mature tRNA while causing accumulation of precursor species retaining both 5'-leader and 3'-trailer sequences, consistent with impaired maturation. In parallel, the nuclear 5'[->]3' exonuclease XRN2 selectively degrades the residual mature hypomodified tRNA pool without affecting precursor accumulation. Loss of mature tRNA activates the integrated stress response and impairs proliferation, which is restored by XRN2 co-depletion. Together, our findings identify m{superscript 1}A58 as a coordinator of human initiator-tRNA maturation and surveillance, establishing a two-step pathway that maintains tRNA homeostasis in human cells.

biochemistry↗

bioRxiv2026

Design and characterization of SAKe, a new building block for protein self-assembly

The nanofabrication of functional protein-based surfaces is challenging due to the chemical complexity of proteins and their unpredictable behavior at the solid-liquid interface. Many proteins of interest -such as antibodies or large enzymatic complexes - lack strong and dynamic protein-protein and protein-surface interactions necessary to drive self-assembly of stable arrays with high surface coverage. Additionally, adsorption-induced conformational changes at the solid-liquid interface could lead to a loss of activity and increase the risk of undesirable interfacial processes. Here we introduce SAKe, a kelch-like designer protein, as a versatile platform to address these challenges. Ancestral sequence reconstruction led to high thermal stability, and the high symmetry allowed modularity of the proteins core. Rational engineering of the bottom side allowed SAKe to form large (up to 5 micrometers in length), well-defined and pH-dependent two-dimensional assemblies while maintaining structural integrity, which is key for further development of functional materials. SAKe self-assembly was investigated through in-liquid atomic force microscopy on muscovite mica. High resolution imaging confirmed the integrity of the SAKe protein upon adsorption on the solid-liquid interface. These results showcase the SAKe protein as a platform for the further engineering of functional protein-based two-dimensional materials.

bioengineering↗

bioRxiv2025

The mammalian rapid tRNA decay pathway is critical for N⁷-methylguanosine-hypomodified tRNA degradation under physiological conditions

Chemical modifications of transfer RNAs (tRNAs) are integral to their stability and to translation. Loss of N7-methylguanosine (m7G) on specific tRNAs reduces their steady-state abundance and impairs translation in mammals, but whether these decreases reflect active degradation under physiological growth conditions is unresolved. Here, using human HCT116 cells, we show that knockdown of the 5'[->]3' exonuclease, XRN2, restores tRNA levels diminished by METTL1 depletion. Leveraging conditional protein knockdown, we performed time-resolved measurements of mature tRNA levels and directly quantified decay kinetics. We show that in the absence of heat stress, mG-hypomodified tRNAs undergo XRN2-dependent accelerated decay. Finally, partial loss of the Drosophila XRN2 ortholog, Rat1, genetically rescues male sterility of mettl1 mutants, demonstrating organismal relevance. These findings define a conserved constitutive rapid tRNA decay pathway in mammals and indicate inhibition of tRNA decay as a potential therapeutic strategy in disorders caused by tRNA hypomodification.

molecular biology↗

bioRxiv2025

Membrane constriction by dynamin through GTP-driven conformational changes from coarse-grained molecular dynamics simulations

Dynamin, a GTPase involved in membrane remodeling processes, plays a pivotal role in membrane fission during endocytosis. Understanding the molecular mechanisms of dynamin assembly and its conformational change triggered by GTP hydrolysis on lipid membranes is crucial for elucidating the intricate details of membrane constriction and fission events. However, the size and complexity of the dynamin assembly prevent us from obtaining comprehensive molecular mechanisms. In this study, we performed coarse-grained molecular dynamics (CG-MD) simulations to elucidate the chemo-mechanical coupling mechanism of dynamin membrane constriction. We set up a CG Martini simulation system that contains dynamin rings on a tubular membrane with realistic molecular structures. Controlling the length of the tubular membrane with a pressure coupling, we simulate membrane constriction through the nucleotide-state-dependent conformational change of dynamin. The simulation results suggest that the conformational change to the GDP state loosens and expands the dynamin rings, resulting in membrane constriction in the protein-uncoated region. This study lays the groundwork for simulating the chemo-mechanical coupling of dynamin-mediated membrane constriction. TOC GRAPHICS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/675253v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@3080b3org.highwire.dtl.DTLVardef@519814org.highwire.dtl.DTLVardef@d76b0forg.highwire.dtl.DTLVardef@b5e4ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Hybridization during the adaptive radiation of Oxera (Lamiaceae) in New Caledonia: Is flower shape shift driven by introgression?

Recent genomic studies have suggested that hybridization may play a significant role in adaptive radiation, rapid speciation, and convergent evolution. The genus Oxera, a plant taxon thought to have diversified at its beginning through adaptive radiation in New Caledonia, provided an opportunity to investigate these processes. Within the robusta subclade of Oxera, characterized by bird-pollinated yellow-orange flowers, convergent evolution of flower shape is likely to have occurred. We aimed to elucidate the hybridization history of the robusta subclade by whole genome sequencing and MIG-seq data. Our analyses revealed an ancestral introgression from O. coriacea to O. sympatrica, whose flowers are remarkably similar to each other. Among the introgressed genomic regions, we identified several genes potentially involved in flower shape development. O. sympatrica and its sympatric sister species exhibit distinct flower shapes, and pollinator-mediated reproductive isolation presumed to be a major barrier between them. The ancestral introgression uncovered in this study may have driven the convergent evolution of flower shape in the robusta subclade and played a crucial role in the speciation process of O. sympatrica. These finding contribute to our understanding of the interplay between hybridization, adaptive radiation, and speciation process.

evolutionary biology↗

bioRxiv2025

Chromosomal fusions and subsequent rearrangements shaped octopus genomes

Why some animal groups retain ancestral chromosomal complements while others change significantly is a fundamental question in evolutionary genomics. Few systems exist where accumulations of chromosomal changes can be studied in the context of morphological innovation. In coleoid cephalopods (octopus, squid, cuttlefish), an ancient coleoid chromosomal rearrangement event (ACCRE) has led to a substantial increase in the chromosome number and a new set of chromosomal homologies. Compared to typical molluscan or bilaterian genomes, ACCRE has enabled the origin of many novel regulatory regions in coleoid cephalopods. However, the discrepancies between extant octopodiform (octopus, [~]30 chromosomes) and decapodiform (squid and cuttlefish, [~]46 chromosomes) karyotypes and the direction of these evolutionary changes remain unexplained. Here we provide a draft genome assembly of the vampire squid Vampyroteuthis sp., the largest cephalopod genome sequenced to-date (over 10 gigabasepairs). Through syntenic comparisons, we infer that this basally branching octopodiform species shows partial retention of the chromosomal complement of Decapodiformes, indicating its more ancestral state and the derived nature of the octopod karyotype. Together with the analysis of a new chromosome-level assembly of the pelagic octopod Argonauta hians, we identified irreversible chromosomal fusion-with-mixing events followed by inter-chromosomal translocations in octopods. We show that this secondary reduction and mixing within octopod chromosomes has enabled the origin of a more entangled genomic configuration, shedding light onto the early evolutionary transitions within the clade. Our results offer broader insights into general patterns of chromosomal evolution following large-scale rearrangement events in animal genomes. Significance statementHow changes to the ancient animal synteny result in novel chromosomal homologies is difficult to dissect due to the lack of intermediate states. Here we report that the genome of Vampyroteuthis, one of the largest animal genomes sequenced to-date (over 11 gigabasepairs), despite its phylogenetic position within the octopodiform cephalopods, partially retains squid and cuttlefish chromosomal complement, reflecting an ancestral karyotypic state that existed at the time of divergence between these cephalopod lineages. Our findings reveal karyotype reductions through chromosomal fusions were followed by inter-chromosomal translocations in octopods, leading to a more specialized genomic and gene regulatory architecture. These data show how chromosomal fusions can act as drivers of further inter-chromosomal rearrangements in animal genomes.

genomics↗

bioRxiv2024

Compartmentalization of Transcripts During Antibody Mediated Rejection in Renal Transplants

We used Digital Spatial Profiling to localize transcripts in glomeruli and tubulointerstitial compartments in a series of 4 biopsies from a patient diagnosed with acute antibody-mediated rejection (AMR). The 4 biopsies included: a baseline protocol biopsy 25 days after transplantation; a 3 month biopsy diagnosed as acute AMR; a biopsy 4 months after treatment with intravenous immunoglobulin (IVIg) showing ongoing AMR with a mild increase in tubulointerstitial fibrosis; and a biopsy 7 months later with resolution of glomerulitis. Glomeruli were captured in regions of interest (ROIs) for whole exome sequencing. Compared to baseline glomeruli, 17 transcripts were increased and 39 decreased in the 3 subsequent biopsies (> 2-fold and p < 0.005). Increased signatures for macrophages correlated with increased numbers of CD68 positive cells imaged in the corresponding glomeruli. The Human Cell Atlas classified the 39 transcripts decreased during the initial rejection as characteristic of podocytes and this gene signature did not recover in the subsequent 2 biopsies. Additional ROIs encompassing areas of tubulointerstitial fibrosis disclosed signatures for memory B cells in the acute AMR sample. Treatment with IVIg did not eliminate the B cell signal in the subsequent biopsy. Collectively these data demonstrate a compartmentalization of injury processes. Innate immune cells including macrophages were located in glomerular and tubulointerstitial compartments, whereas, adaptive immune cells including memory B cells localized to the tubulointerstitial compartment. Furthermore, podocyte transcripts were decreased in glomeruli and did not recover with treatment indicating a vulnerability of these cells to acute AMR.

pathology↗

bioRxiv2024

Adolescent Seizure Impacts Oligodendrocyte Development, Neuronal-Glial Circuit Formation, and Myelination

Myelin sheaths, formed by oligodendrocyte cells in the CNS, are vital for rapid conduction of electrical signals down neuronal axons. Oligodendrocyte progenitors differentiate and myelinate axons during development and following demyelinating injury. However, the mechanisms that drive the timing and specificity of developmental myelination are not well understood. It is known that oligodendrocyte progenitors receive synapses from neurons, providing a potential mechanism for neuronal-glial communication. We have previously shown that changing neuronal activity affects the proliferation of oligodendrocyte cells and neuron to OPC connections. We hypothesized that OPC proliferation and differentiation would be affected by pathological neuronal activity during adolescent development, when developmental myelination is occurring, and that this would also impact neuron to OPC connectivity and myelination. We used kainic acid to induce a seizure, then analyzed changes in the rate of OPC proliferation and differentiation five days later in the cerebral cortex, corpus callosum, and hippocampus. We found that OPC proliferation increased, the overall numbers of OPCs increased, and the number of mature oligodendrocytes decreased. We measured changes in the myelination to determine whether seizure activity directly affected myelination rate in adolescent development, and found decreased myelin in the cerebral cortex, corpus callosum, and hippocampus. We used viral monosynaptic circuit tracing to determine whether connections between neurons and OPCs were affected by seizure activity, and found a decrease in neuron to OPC connections in seizure mice compared to controls. Finally, we measured changes in the presence of kir4.1 potassium channels in OPCs, an important regulator of OPC membrane potential as well as an ion channel important for myelination, and found that there was a decrease in the number of potassium channels on OPCs after adolescent seizure. These findings provide insight into the response of the adolescent brain to seizure activity, as well as how seizures affect neuronal glial connections, OPC development and myelin formation, with the goal of understanding how these mechanisms may be important for treatment of demyelination after seizure and in epilepsy.

neuroscience↗

bioRxiv2023

Mettl1-dependent m7G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster

N7-methylguanosine (m7G) in the variable loop region of tRNA is catalyzed by METTL1/WDR4 heterodimer and stabilizes target tRNA. Here, we reveal essential functions of Mettl1 in Drosophila fertility. Knockout of Mettl1 (Mettl1-KO) lost the elongated spermatids and mature sperm, which was fully rescued by a Mettl1-transgene expression, but not a catalytic-dead Mettl1 transgene. This demonstrates that Mettl1-dependent m7G is required for spermatogenesis. Mettl1-KO resulted in a loss of m7G modification on a subset of tRNAs and a decreased level of tRNA expression. Strikingly, overexpression of the translational elongation factor, EF11, which can compete with the rapid tRNA decay (RTD) pathway in S. cerevisiae, significantly counteracted the sterility of Mettl1-KO males, supporting a critical role of m7G modification of tRNAs in spermatogenesis. Ribosome profiling showed that Mettl1-KO led to the ribosome stalling at codons decoded by tRNAs that were reduced in expression. Mettl1-KO also significantly reduced the translation efficiency of genes involved in elongated spermatid formation and sperm stability. These findings reveal a developmental role for m7G tRNA modifications and indicate that m7G modification-dependent tRNA stability differs among tissues.

molecular biology↗

bioRxiv2023

Shh from mossy cells contributes to preventing NSC pool depletion after seizure-induced neurogenesis and in aging

Epileptic seizures induce aberrant neurogenesis from resident neural stem cells (NSCs) in the dentate gyrus of the adult mouse hippocampus, which has been implicated in depletion of the NSC pool and impairment of hippocampal function. However, the mechanisms regulating neurogenesis after seizures remain unknown. Here we demonstrate that Shh from mossy cells is a major source of Shh signaling activity after seizures, by which mossy cells contribute to seizure-induced neurogenesis and maintenance of the NSC pool. Deletion of Shh from mossy cells attenuates seizure-induced neurogenesis. Moreover, in the absence of Shh from mossy cells, NSCs pool are prematurely depleted after seizure-induced proliferation, and NSCs have impaired self-renewal. Likewise, lack of Shh from mossy cells accelerates age-related decline of the NSC pool with accompanying reduction of self-renewal of NSCs outside the context of pathology such as seizures. Together, our findings indicate that Shh from mossy cells is critical to maintain NSCs and to prevent exhaustion from excessive consumption in aging and after seizures.

neuroscience↗

bioRxiv2023

Pulsed ultrasound promotes secretion of anti-inflammatory extracellular vesicles from skeletal myotubes via elevation of intracellular calcium level

The regulation of inflammatory responses is an important intervention in biological function and macrophages play an essential role during inflammation. Skeletal muscle is the largest organ in the human body and releases various factors which mediate anti-inflammatory/immune modulatory effects. Recently, the roles of extracellular vesicles (EVs) from a large variety of cells are reported. In particular, EVs released from skeletal muscle are attracting attention due to their therapeutic effects on dysfunctional organs and tissues. Also, ultrasound (US) promotes release of EVs from skeletal muscle. In this study, we investigated the output parameters and mechanisms of US-induced EV release enhancement and the potential of US-treated skeletal muscle-derived EVs in the regulation of inflammatory responses in macrophages. High-intensity US (3.0 W/cm2) irradiation increased EV secretion via elevating intracellular Ca2+ level without negative effects. Moreover, US-induced EVs suppressed expression levels of pro-inflammatory factors in macrophages. miRNA sequencing analysis revealed that miR-206-3p and miR-378a-3p were especially abundant in skeletal myotube-derived EVs. In this study we demonstrated that high-intensity US promotes the release of anti-inflammatory EVs from skeletal myotubes and exert anti-inflammatory effects on macrophages.

immunology↗

bioRxiv2022

Neuronal Activity Alters Neuron to OPC Synapses

The mechanisms that drive the timing and specificity of oligodendrocyte myelination during development, or remyelination after injury or immune attack are not well understood. Recent work has shown that oligodendrocyte progenitors receive synapses from neurons, providing a potential mechanism for neuronal-glial communication. We hypothesize that these connections are important both for correct myelination of neurons during development and for myelination during neuronal plasticity. We utilized chemogenetic tools and viral monosynaptic circuit tracing to analyze these neuroglial connections and to examine OPC proliferation, myelination, synapse formation, and neuronal-glial connectivity after increasing or decreasing neuronal activity in vivo. We found that increasing neuronal activity increased OPC activation, but not proliferation. We also found that altering neuronal activity altered neuronal-glial synaptic connections: while it did not impact the total number of neuronal inputs, or the number of inhibitory neuronal inputs, it did alter the number of excitatory neuron to OPC connections. We also found that increasing or decreasing neuronal activity impacted the ratio of excitatory and inhibitory synapses. Our data show that neuronal activity affects OPC activation, neuronal synapse formation onto OPCs, as well as the types of neuronal inputs to OPCs, indicating that neuronal activity is important for OPC circuit composition and function.

neuroscience↗

bioRxiv2021

Profiling a single-stranded DNA region within an rDNA segment that is a loading site for bacterial condensin

Bacterial condensin preferentially loads to single-stranded DNA (ssDNA) in vitro and loads onto rDNA in vivo to support proper chromosome compaction. Thus, the actively transcribing rDNA would provide the ssDNA region for the topological loading of bacterial condensin. We attempted to detect the ssDNA region in the rrnI gene in situ. Non-denaturing sodium bisulfite treatment catalyzed the conversion of cytosines to thymines via uracils (CT-conversion) at locally melted DNA of a bacterial genome. Using next-generation sequencing, we generated an average of 11,000 reads covering each cytosine on the PCR-amplified rDNA segment to obtain the actual CT-conversion rate. In principle, the CT-conversion rate is an accurate guide to detect the formation of the ssDNA segment. We expected that an increment of the CT-conversion rate would reflect a trend toward ssDNA accumulation at a given site within the rDNA. We detected multiple ssDNA segments throughout the rDNA. The deletion mutations of the rDNA that affect the bacterial-condensin loading hindered the ssDNA formation only at the 100-500 bp segment downstream of the promoter. These data support the idea that the ssDNA segment plays a crucial role as the bacterial condensin-loading site and suggest the mechanism of condensin loading onto rDNA.

molecular biology↗

bioRxiv2020

Shape and size complementarity induced formation of supramolecular protein assemblies with metal-oxo clusters

The controlled formation of protein supramolecular assemblies is challenging but it could provide an important route for the development of hybrid biomaterials. In this work, we demonstrate formation of well-defined complexes formed between the 8-fold symmetrical designer protein Tako8 and soluble metal-oxo clusters from the family of Anderson-Evans, Keggin and ZrIV- substituted Wells-Dawson polyoxometalates. A combination of x-ray crystallography and solution studies showed that metal-oxo clusters are able to serve as linker nodes for the bottom-up creation of protein based supramolecular assemblies. Our findings indicate that clusters with larger size and negative charge are capable of modulating the crystal packing of the protein, highlighting the need for a size and shape complementarity with the protein node for optimal alteration of the crystalline self-assembly.

biochemistry↗

bioRxiv2020

NMDA receptors control cortical axonal projections via EPHRIN-B/EPHB signaling

Callosal projections from primary somatosensory cortex (S1) are key for processing somatosensory inputs and integrating sensory-motor information. How the callosal innervation pattern in S1 is formed during early postnatal development is not clear. We found that the normal termination pattern of these callosal projections is disrupted in cortex specific NMDAR mutants. Rather than projecting selectively to the primary/secondary somatosensory cortex (S1/S2) border, axons were uniformly distributed throughout S1. In addition, the density of this projection increased over postnatal life until the mice died by P30. By combining genetic and antibody-mediated loss of function, we demonstrated that it is NR2B-containing NMDA receptors in target S1 that mediate this guidance phenotype, thus playing a central role in interhemispheric connectivity. Furthermore, we found that this function of NMDA receptors in callosal circuit formation is independent of ion channel function and instead depends on interactions with EPHRIN-B/EPHB. Thus, NMDAR cooperates with EPHRIN-B/EPHB in target S1 to control the formation callosal circuits by acting as an accessory axon guidance receptor modulating EPH-dependent repulsion.

neuroscience↗

bioRxiv2019

Large DNA virus promoted the endosymbiotic evolution to make a photosynthetic eukaryote

Chloroplasts in photosynthetic eukaryotes originated from a cyanobacterial endosymbiosis far more than 1 billion years ago1-3. Due to this ancientness, it remains unclear how this evolutionary process proceeded. To unveil this mystery, we analysed the whole genome sequence of a photosynthetic rhizarian amoeba4, Paulinella micropora5,6, which has a chloroplast-like organelle that originated from another cyanobacterial endosymbiosis7-10 about 0.1 billion years ago11. Here we show that the predacious amoeba that engulfed cyanobacteria evolved into a photosynthetic organism very quickly in the evolutionary time scale, probably aided by the drastic genome reorganization activated by large DNA virus. In the endosymbiotic evolution of eukaryotic cells, gene transfer from the endosymbiont genome to the host nucleus is essential for the evolving host cell to control the endosymbiont-derived organelle12. In P. micropora, we found that the gene transfer from the free-living and endosymbiotic bacteria to the amoeba nucleus was rapidly activated but both simultaneously ceased within the initiation period of the endosymbiotic evolution, suggesting that the genome reorganization drastically proceeded and completed. During this period, large DNA virus appeared to have infected the amoeba, followed by the rapid amplification and diversification of virus-related genes. These findings led us to re-examine the conventional endosymbiotic evolutionary scenario that exclusively deals with the host and the symbiont, and to extend it by incorporating a third critical player, large DNA virus, which activates the drastic gene transfer and genome reorganization between them. This Paulinella version of the evolutionary hypothesis deserves further testing of its generality in evolutionary systems and could shed light on the unknown roles of large DNA viruses13 in the evolution of terrestrial life.

evolutionary biology↗

bioRxiv2018

Suppressor of Fused controls perinatal expansion and quiescence of future dentate adult neural stem cells

Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. The establishment and maintenance of quiescent NSC pools during development is not understood. Here we show that Suppressor of Fused (Sufu) controls establishment of the quiescent NSC pool during mouse dentate gyrus (DG) development through regulation of Sonic Hedgehog (Shh) signaling. Deletion of Sufuin NSCs at the beginning of DG development decreases Shh signaling leading to reduced proliferation of NSCs, resulting in a small quiescent NSC pool in adult mice. We found that putative adult NSCs proliferate and increase their numbers in the first postnatal week and subsequently become quiescent towards the end of the first postnatal week. In the absence of Sufu, postnatal expansion of NSCs is compromised, and NSCs prematurely become quiescent. Thus, Sufu is required for Shh signaling activity ensuring the expansion and proper transition of NSC pools to quiescence during DG development.

developmental biology↗

bioRxiv2018

Suppressor of Fused controls the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism

The ventricular-subventricular zone (V-SVZ) of the forebrain is the source of neurogenic stem/precursor cells for adaptive and homeostatic needs throughout the life of most mammals. Here, we report that Suppressor of Fused (SUFU) plays a critical role in the establishment of the V-SVZ at early neonatal stages by controlling the proliferation of distinct subpopulations of stem/precursor cells. Conditional deletion of Sufu in radial glial progenitor cells (RGCs) at E13.5 resulted in a dramatic increase in the proliferation of Sox2+ Type B cells, as well as Gsx2+ ventral forebrain derived transit amplifying precursor cells (TACs). In contrast, we found a significant decrease in Tbr2+ dorsal forebrain derived TACs indicating that innate differences between dorsal and ventral forebrain derived Type B cells influence Sufu function. However, most precursors failed to survive and accumulated in the dorsal V-SVZ, demonstrating that precursors are unable to transition into functional differentiated progenies. These defects were accompanied by reduced Gli3 expression, yet despite reduced Gli3 levels, activation of Sonic hedgehog (Shh) signaling did not occur implying that the Sufu-Gli3 regulatory axis may influence other signaling pathways in the neonatal dorsal V-SVZ. These data suggest that Sufu plays a critical role in controlling Gli3 function in the establishment and survival of functional stem/precursor cells in the postnatal dorsal V-SVZ.\n\nSUMMARY STATEMENTConditional deletion of Sufu cause dramatic expansion of neural stem/precursor cells in the neonatal ventricular-subventricular (SVZ) zone. This defect occurs through a Gli3-dependent mechanism that results in the downregulation of Shh signaling.

developmental biology↗