@unpublished{21212, abstract = {Malignant glioma is incurable. Using a mouse genetic mosaic system to generate sporadic Trp53,Nf1-null OPCs, we previously identified oligodendrocyte precursor cell (OPC) as a cell-of-origin of glioma. Here, we report that pre-malignant Trp53,Nf1-null OPCs outcompete wildtype counterparts during their expansion. Blocking competition by mutating/strengthening wildtype OPCs impeded both pre-malignant progression and malignant expansion of glioma. “In-tissue” phosphoproteomic profiling revealed an enrichment of phosphopeptides related to RNA splicing and protein translation at the peak of cell competition, suggesting that competitiveness may stem from unique protein species. Among candidates was mTORC1, whose pharmacological inhibition or genetic disruption resulted in a loss of competitiveness in our mouse model. Finally, analysis of patient biopsies and interrogating the role of individual gliomagenic mutations in OPC competition supported its relevance in human gliomas. Together, these findings identified the driving role of competitive interactions among OPCs in gliomagenesis, and suggest unconventional therapeutic strategies to target this process.}, author = {Jiang, Ying and Ahn, Ryuhjin and Huang, Arthur and Gonzalez, Phillippe P. and Kim, Jungeun and Zhang, Guoxin and Liu, Zihao and He, Zhenqiang and Dudley, Lindsey and Patel, Kunal S. and Dzhivhuho, Godfrey A. and Crowl, Sam and Przanowski, Piotr and Camacho, Luisa Quesada and Hao, Sijie and Zeng, Jianhao and Hippenmeyer, Simon and Fallahi-Sichani, Mohammad and Janes, Kevin A. and Naegle, Kristen M. and Hammarskjold, Marie-Louise and Goldman, Steven A. and Kornblum, Harley I. and Yao, Maojin and White, Forest and Zong, Hui}, booktitle = {bioRxiv}, title = {{Critical role of cell competition in gliomagenesis}}, doi = {10.64898/2026.01.15.699808}, year = {2026}, } @unpublished{21290, abstract = {Gene duplication underlies evolutionary innovation, yet many paralogues remain highly similar, raising questions about their functional divergence and physiological relevance. The spliceosomal Sm core protein SNRPB and its mammalian-specific paralogue SNRPN share over 90% sequence identity, but their distinct expression patterns - SNRPB being ubiquitous and SNRPN confined to the brain - suggest specialized functions. Why mammals have two different spliceosomes has remained obscure. Here, we generated isogenic human cell lines expressing ectopically either SNRPB or SNRPN exclusively and found that SNRPN stabilizes transcripts involved in energy metabolism and mitochondrial function, leading to increased mitochondrial abundance and oxygen consumption. Despite similar spliceosomal interactomes, SNRPN more strongly associates with the PRMT5 methylosome complex and exhibits dynamic arginine methylation in its C-terminal region that is sensitive to translation inhibition and amino acid availability. The SNRPN-dependent transcriptome responds to translation inhibition by stabilizing long, intron-rich genes involved in amino acid and energy metabolism. Our findings reveal a nutrient-sensitive, methylation-dependent mechanism that differentiates the two paralogues. This suggests that SNRPN functions as a metabolic-specialized spliceosomal subunit thereby providing tissue-specific adaptation of RNA processing in mammals.}, author = {Polat Haas, Feyza and Villalba Requena, Ana and Rusina, Polina and Gopalan, Anusha and Fritz, Hector and Akhmetkaliyev, Azamat and Ruehle, Frank and Einsiedel, Anna and Szczepinska, Anna and Kielisch, Fridolin and Chen, Jia-Xuan and Nguyen, Susanne and Schmidlin, Thierry and Hippenmeyer, Simon and Bailicata, M. Felicia and Keller Valsecchi, Claudia Isabelle}, booktitle = {bioRxiv}, title = {{The splicing paralogues SNRPB and SNRPN control differential metabolic states.}}, doi = {10.64898/2026.02.11.705284}, year = {2026}, } @unpublished{21291, abstract = {The complexity and specificity of movement in vertebrates is driven by a rich diversity of spinal motor and interneuron cell types. During development, eleven spinal cord progenitor domains generate an equivalent number of cardinal neuron types. How progenitor domains, individual progenitors, and post-mitotic diversity relate is still unknown. We performed high-resolution, single-progenitor cell lineage tracing in the embryonic mouse spinal cord using mosaic analysis with double markers (MADM). Our quantitative study of lineage progression revealed that spinal cord progenitors undergo highly variable numbers of proliferative, neurogenic, and gliogenic cell divisions. The nascent clonally-related neurons migrate radially over large distances, span the dorsoventral axis, and even cross the midline, demonstrating striking bilaterality. Molecular and morphometric analysis indicate high levels of progenitor multipotency, with an individual progenitor capable of producing several molecularly and morphologically distinct neuron types, as well as astrocytes. These findings redefine spinal cord development as a process in which lineage variability — rather than rigid progenitor identity — drives the generation of cellular diversity.}, author = {Gobeil, Sophie A and Da Silveira Neto, Francisco and Silvestrelli, Giulia and Smits, Matthijs Geert and Streicher, Carmen and Cheung, Giselle T and Hippenmeyer, Simon and Sweeney, Lora Beatrice Jaeger}, booktitle = {bioRxiv}, title = {{Lineage origin of spinal cord cell type diversity}}, doi = {10.64898/2026.02.12.705305}, year = {2026}, } @article{14647, abstract = {In the developing vertebrate central nervous system, neurons and glia typically arise sequentially from common progenitors. Here, we report that the transcription factor Forkhead Box G1 (Foxg1) regulates gliogenesis in the mouse neocortex via distinct cell-autonomous roles in progenitors and postmitotic neurons that regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate that loss of Foxg1 in cortical progenitors at neurogenic stages causes premature astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway component Fgfr3, which is suppressed by FOXG1 cell-autonomously to maintain neurogenesis. Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the augmentation of FGF signalling. We identify a second novel function of FOXG1 in regulating the expression of gliogenic cues in newborn neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons non-autonomously enhances gliogenesis in the progenitors via FGF signalling. These results fit well with the model that newborn neurons secrete cues that trigger progenitors to produce the next wave of cell types, astrocytes. If FGF signalling is attenuated in Foxg1 null progenitors, they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic signalling via the FGF pathway to regulate the sequential generation of neurons, astrocytes, and oligodendrocytes in the cerebral cortex. }, author = {Bose, Mahima and Suresh, Varun and Mishra, Urvi and Talwar, Ishita and Yadav, Anuradha and Biswas, Shiona and Hippenmeyer, Simon and Tole, Shubha}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway}}, doi = {10.7554/elife.101851.3}, volume = {13}, year = {2025}, } @inbook{18765, abstract = {Mosaic Analysis with Double Markers (MADM) represents a mouse genetic approach coupling differential fluorescent labeling to genetic manipulations in dividing cells and their lineages. MADM uniquely enables the generation and visualization of individual control or homozygous mutant cells in a heterozygous genetic environment. Among its diverse applications, MADM has been used to dissect cell-autonomous gene functions important for cortical development and neural development in general. The high cellular resolution offered by MADM also permits the analysis of transcriptomic changes of individual cells upon genetic manipulations. In this chapter, we describe an experimental protocol combining the generation and isolation of MADM-labeled cells with downstream single-cell RNA-sequencing technologies to probe cell-type specific phenotypes due to genetic mutations at single-cell resolution.}, author = {Cheung, Giselle T and Pauler, Florian and Hippenmeyer, Simon}, booktitle = {Lineage Tracing}, editor = {Garcia-Marques, Jorge and Lee, Tzumin}, isbn = {9781071643099}, issn = {1940-6029}, pages = {139--151}, publisher = {Springer Nature}, title = {{Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM)}}, doi = {10.1007/978-1-0716-4310-5_7}, volume = {2886}, year = {2025}, } @unpublished{19717, abstract = {Radial glial progenitors (RGPs) generate all projection neurons (PNs) in the cerebral cortex through incompletely understood processes. Herein, we combine Mosaic Analysis with Double Markers (MADM)-based clonal analysis at embryonic days 12.5 and 13.5 with early postnatal callosal tracing to reveal a lineage progression that challenges the inside-outside model of cortical development and the conventional view of an invariable sequence of asymmetric neurogenic divisions. Our data demonstrate that early multipotent RGPs generate all extra-telencephalic (ET) and intra-telencephalic (IT) PNs across all layers through parallel sublineages and the random specification, during the earliest neurogenic divisions, of fate-restricted daughter RGPs. While the neuronal production of the parental multipotent RGPs consists of small ET-PN or IT-PN outputs, fate-restricted RGPs produce larger translaminar outputs spanning deep and upper layers of only IT-PNs, the predominant mammalian PN subtype. We further show that the emergence of IT-PN fate-restricted RGPs also leads to quantitatively and temporally stereotyped neurogenesis population-wise.}, author = {Varela-Martínez, I and Villalba Requena, Ana and Garcia-Marqués, J. and Hippenmeyer, Simon and Nieto, M.}, booktitle = {bioRxiv}, title = {{Early emergence of projection-subtype fate-restricted radial glial progenitors orchestrates neocortical neurogenesis}}, doi = {10.1101/2025.05.07.652665}, year = {2025}, } @article{8616, abstract = {The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain.}, author = {Gao, Xiaofei and Li, Jun-Liszt and Chen, Xingjun and Ci, Bo and Chen, Fei and Lu, Nannan and Shen, Bo and Zheng, Lijun and Jia, Jie-Min and Yi, Yating and Zhang, Shiwen and Shi, Ying-Chao and Shi, Kaibin and Propson, Nicholas E and Huang, Yubin and Poinsatte, Katherine and Zhang, Zhaohuan and Yue, Yuanlei and Bosco, Dale B and Lu, Ying-mei and Yang, Shi-bing and Adams, Ralf H. and Lindner, Volkhard and Huang, Fen and Wu, Long-Jun and Zheng, Hui and Han, Feng and Hippenmeyer, Simon and Stowe, Ann M. and Peng, Bo and Margeta, Marta and Wang, Xiaoqun and Liu, Qiang and Körbelin, Jakob and Trepel, Martin and Lu, Hui and Zhou, Bo O. and Zhao, Hu and Su, Wenzhi and Bachoo, Robert M. and Ge, Woo-ping}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Reduction of neuronal activity mediated by blood-vessel regression in the brain}}, doi = {10.1038/s41467-025-60308-0}, volume = {16}, year = {2025}, } @article{19718, abstract = {The cerebral cortex is arguably the most complex organ in humans. The cortical architecture is characterized by a remarkable diversity of neuronal and glial cell types that make up its neuronal circuits. Following a precise temporally ordered program, radial glia progenitor (RGP) cells generate all cortical excitatory projection neurons and glial cell-types. Cortical excitatory projection neurons are produced either directly or via intermediate progenitors, through indirect neurogenesis. How the extensive cortical cell-type diversity is generated during cortex development remains, however, a fundamental open question. How do RGPs quantitatively and qualitatively generate all the neocortical neurons? How does direct and indirect neurogenesis contribute to the establishment of neuronal and lineage heterogeneity? Whether RGPs represent a homogeneous and/or multipotent progenitor population, or if RGPs consist of heterogeneous groups is currently also not known. In this review, we will summarize the latest findings that contributed to a deeper insight into the above key questions.}, author = {Pipicelli, Fabrizia and Villalba Requena, Ana and Hippenmeyer, Simon}, issn = {0959-4388}, journal = {Current Opinion in Neurobiology}, publisher = {Elsevier}, title = {{How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex}}, doi = {10.1016/j.conb.2025.103046}, volume = {93}, year = {2025}, } @unpublished{19762, abstract = {The cerebral cortex must contain the appropriate numbers of neurons in each layer to acquire its proper functional organization. Accordingly, neurogenesis requires precise regulation along development. Cortical neurons are made either directly by Radial Glia Cells (RGCs) that self- consume, or indirectly from RGCs via Intermediate Progenitor Cells (IPCs) and largely preserving the RGC pool. According to the standing model of cortical development, Direct Neurogenesis predominates at early stages of development, and progressively shifts to Indirect Neurogenesis, which predominates at late stages. However, neurogenesis at early stages should be compatible with RGC amplification, and neurogenesis at late stages needs to involve RGC consumption, which seems in conflict with the standing model. Here we studied the modes of neurogenesis along cortical development using multiple approaches, including birthdating, live imaging and MADM clone labeling. Contrary to the established dogma, our data show that Indirect Neurogenesis clearly predominates at early developmental stages, gradually shifting to Direct Neurogenesis at late stages. These findings challenge the current model of cortical neurogenesis, and prompt a re-evaluation of previous and ongoing work about the genetic and molecular mechanisms regulating this process.}, author = {Cárdenas, Adrián and Çelik, Irem and Espinós, Alexandre and Streicher, Carmen and López-González, Lara and del-Valle-Anton, Lucia and Fernández, Virginia and Amin, Salma and Negri, Enrico and Ortuño, Eduardo Fernández and Hippenmeyer, Simon and Borrell, Víctor}, booktitle = {bioRxiv}, title = {{Early indirect neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex development}}, doi = {10.1101/2025.05.22.655488}, year = {2025}, } @article{14794, abstract = {Mosaic analysis with double markers (MADM) technology enables the sparse labeling of genetically defined neurons. We present a protocol for time-lapse imaging of cortical projection neuron migration in mice using MADM. We describe steps for the isolation, culturing, and 4D imaging of neuronal dynamics in MADM-labeled brain tissue. While this protocol is compatible with other single-cell labeling methods, the MADM approach provides a genetic platform for the functional assessment of cell-autonomous candidate gene function and the relative contribution of non-cell-autonomous effects. For complete details on the use and execution of this protocol, please refer to Hansen et al. (2022),1 Contreras et al. (2021),2 and Amberg and Hippenmeyer (2021).3}, author = {Hansen, Andi H and Hippenmeyer, Simon}, issn = {2666-1667}, journal = {STAR Protocols}, number = {1}, publisher = {Elsevier}, title = {{Time-lapse imaging of cortical projection neuron migration in mice using mosaic analysis with double markers}}, doi = {10.1016/j.xpro.2023.102795}, volume = {5}, year = {2024}, } @article{12875, abstract = {The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny.}, author = {Cheung, Giselle T and Pauler, Florian and Koppensteiner, Peter and Krausgruber, Thomas and Streicher, Carmen and Schrammel, Martin and Özgen, Natalie Y and Ivec, Alexis and Bock, Christoph and Shigemoto, Ryuichi and Hippenmeyer, Simon}, issn = {0896-6273}, journal = {Neuron}, number = {2}, pages = {230--246.e11}, publisher = {Elsevier}, title = {{Multipotent progenitors instruct ontogeny of the superior colliculus}}, doi = {10.1016/j.neuron.2023.11.009}, volume = {112}, year = {2024}, } @article{14683, abstract = {Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1}, author = {Amberg, Nicole and Cheung, Giselle T and Hippenmeyer, Simon}, issn = {2666-1667}, journal = {STAR Protocols}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Neuroscience}, number = {1}, publisher = {Elsevier}, title = {{Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry}}, doi = {10.1016/j.xpro.2023.102771}, volume = {5}, year = {2024}, } @article{17187, abstract = {The generation of diverse cell types during development is fundamental to brain functions. We outline a protocol to quantitatively assess the clonal output of individual neural progenitors using mosaic analysis with double markers (MADM) in mice. We first describe steps to acquire and reconstruct adult MADM clones in the superior colliculus. Then we detail analysis pipelines to determine clonal composition and architecture. This protocol enables the buildup of quantitative frameworks of lineage progression with precise spatial resolution in the brain. For complete details on the use and execution of this protocol, please refer to Cheung et al.1}, author = {Cheung, Giselle T and Streicher, Carmen and Hippenmeyer, Simon}, issn = {2666-1667}, journal = {STAR Protocols}, number = {3}, publisher = {Elsevier}, title = {{Protocol for quantitative reconstruction of cell lineage using mosaic analysis with double markers in mice}}, doi = {10.1016/j.xpro.2024.103157}, volume = {5}, year = {2024}, } @article{17232, abstract = {The lineage relationship of clonally-related cells offers important insights into the ontogeny and cytoarchitecture of the brain in health and disease. Here, we provide a protocol to concurrently assess cell lineage relationship and cell-type identity among clonally-related cells in situ. We first describe the preparation and screening of acute brain slices containing clonally-related cells labeled using mosaic analysis with double markers (MADM). We then outline steps to collect RNA from individual cells for downstream applications and cell-type identification using RNA sequencing. For complete details on the use and execution of this protocol, please refer to Cheung et al. 1}, author = {Cheung, Giselle T and Pauler, Florian and Koppensteiner, Peter and Hippenmeyer, Simon}, issn = {2666-1667}, journal = {STAR Protocols}, number = {3}, publisher = {Elsevier}, title = {{Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq}}, doi = {10.1016/j.xpro.2024.103168}, volume = {5}, year = {2024}, } @inbook{17425, abstract = {Mosaic Analysis with Double Markers (MADM) is a powerful genetic method typically used for lineage tracing and to disentangle cell autonomous and tissue-wide roles of candidate genes with single cell resolution. Given the relatively sparse labeling, depending on which of the 19 MADM chromosomes one chooses, the MADM approach represents the perfect opportunity for cell morphology analysis. Various MADM studies include reports of morphological anomalies and phenotypes in the central nervous system (CNS). MADM for any candidate gene can easily incorporate morphological analysis within the experimental workflow. Here, we describe the methods of morphological cell analysis which we developed in the course of diverse recent MADM studies. This chapter will specifically focus on methods to quantify aspects of the morphology of neurons and astrocytes within the CNS, but these methods can broadly be applied to any MADM-labeled cells throughout the entire organism. We will cover two analyses—soma volume and dendrite characterization—of physical characteristics of pyramidal neurons in the somatosensory cortex, and two analyses—volume and Sholl analysis—of astrocyte morphology.}, author = {Miranda, Osvaldo and Cheung, Giselle T and Hippenmeyer, Simon}, booktitle = {Neuronal Morphogenesis}, editor = {Toyooka, Kazuhito}, isbn = {9781071639689}, issn = {1940-6029}, pages = {283--299}, publisher = {Springer Nature}, title = {{Morphological Analysis of Neurons and Glia Using Mosaic Analysis with Double Markers}}, doi = {10.1007/978-1-0716-3969-6_19}, volume = {2831}, year = {2024}, } @article{12542, abstract = {In this issue of Neuron, Espinosa-Medina et al.1 present the TEMPO (Temporal Encoding and Manipulation in a Predefined Order) system, which enables the marking and genetic manipulation of sequentially generated cell lineages in vertebrate species in vivo.}, author = {Villalba Requena, Ana and Hippenmeyer, Simon}, issn = {1097-4199}, journal = {Neuron}, number = {3}, pages = {291--293}, publisher = {Elsevier}, title = {{Going back in time with TEMPO}}, doi = {10.1016/j.neuron.2023.01.006}, volume = {111}, year = {2023}, } @article{12562, abstract = {Presynaptic inputs determine the pattern of activation of postsynaptic neurons in a neural circuit. Molecular and genetic pathways that regulate the selective formation of subsets of presynaptic inputs are largely unknown, despite significant understanding of the general process of synaptogenesis. In this study, we have begun to identify such factors using the spinal monosynaptic stretch reflex circuit as a model system. In this neuronal circuit, Ia proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle (termed homonymous connections) or muscles with related or synergistic function. However, monosynaptic connections are not formed with motor neurons innervating muscles with antagonistic functions. The ETS transcription factor ER81 (also known as ETV1) is expressed by all proprioceptive afferents, but only a small set of motor neuron pools in the lumbar spinal cord of the mouse. Here we use conditional mouse genetic techniques to eliminate Er81 expression selectively from motor neurons. We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive afferents conveying information from homonymous and synergistic muscles, with no change observed in the connectivity pattern from antagonistic proprioceptive afferents. In summary, these findings suggest a role for ER81 in defined motor neuron pools to control the assembly of specific presynaptic inputs and thereby influence the profile of activation of these motor neurons.}, author = {Ladle, David R. and Hippenmeyer, Simon}, issn = {1522-1598}, journal = {Journal of Neurophysiology}, keywords = {Physiology, General Neuroscience}, number = {3}, pages = {501--512}, publisher = {American Physiological Society}, title = {{Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons}}, doi = {10.1152/jn.00172.2022}, volume = {129}, year = {2023}, } @inbook{14757, abstract = {The cerebral cortex is comprised of a vast cell-type diversity sequentially generated by cortical progenitor cells. Faithful progenitor lineage progression requires the tight orchestration of distinct molecular and cellular mechanisms regulating proper progenitor proliferation behavior and differentiation. Correct execution of developmental programs involves a complex interplay of cell intrinsic and tissue-wide mechanisms. Many studies over the past decades have been able to determine a plethora of genes critically involved in cortical development. However, only a few made use of genetic paradigms with sparse and global gene deletion to probe cell-autonomous vs. tissue-wide contribution. In this chapter, we will elaborate on the importance of dissecting the cell-autonomous and tissue-wide mechanisms to gain a precise understanding of gene function during radial glial progenitor lineage progression.}, author = {Villalba Requena, Ana and Amberg, Nicole and Hippenmeyer, Simon}, booktitle = {Neocortical Neurogenesis in Development and Evolution}, editor = {Huttner, Wieland}, pages = {169--191}, publisher = {Wiley}, title = {{Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression}}, doi = {10.1002/9781119860914.ch10}, year = {2023}, } @article{12679, abstract = {How to generate a brain of correct size and with appropriate cell-type diversity during development is a major question in Neuroscience. In the developing neocortex, radial glial progenitor (RGP) cells are the main neural stem cells that produce cortical excitatory projection neurons, glial cells, and establish the prospective postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated developmental program that when disrupted can result in severe cortical malformations such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms instructing faithful RGP lineage progression are however not well understood. This review will summarize recent conceptual advances that contribute to our understanding of the general principles of RGP lineage progression.}, author = {Hippenmeyer, Simon}, issn = {0959-4388}, journal = {Current Opinion in Neurobiology}, keywords = {General Neuroscience}, number = {4}, publisher = {Elsevier}, title = {{Principles of neural stem cell lineage progression: Insights from developing cerebral cortex}}, doi = {10.1016/j.conb.2023.102695}, volume = {79}, year = {2023}, } @article{12802, abstract = {Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.}, author = {Knaus, Lisa and Basilico, Bernadette and Malzl, Daniel and Gerykova Bujalkova, Maria and Smogavec, Mateja and Schwarz, Lena A. and Gorkiewicz, Sarah and Amberg, Nicole and Pauler, Florian and Knittl-Frank, Christian and Tassinari, Marianna and Maulide, Nuno and Rülicke, Thomas and Menche, Jörg and Hippenmeyer, Simon and Novarino, Gaia}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {9}, pages = {1950--1967.e25}, publisher = {Elsevier}, title = {{Large neutral amino acid levels tune perinatal neuronal excitability and survival}}, doi = {10.1016/j.cell.2023.02.037}, volume = {186}, year = {2023}, }