@unpublished{21290,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@unpublished{19717,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{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},
}

@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},
}

@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},
}