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Temporal and sequential transcriptional dynamics define lineage shifts in corticogenesis.

Tanzila Mukhtar 1, 12. ✱ , Jeremie Breda 2, 3, 12 , Manal A Adam 4, 5, 6 12 , Marcelo Boareto 3, 7, 12 , Pascal Grobecker 2, 3, 12 , Zahra Karimaddini 3, 7, 12 , Alice Grison 1, 12 , Katja Eschbach 8 , Ramakrishnan Chandrasekhar 9 , Swen Vermeul 10 , Michal Okoniewski 10 , Mikhail Pachkov 2, 3 , Corey C Harwell 4, 5, 6 , Suzana Atanasoski 1, 11, 13 , Christian Beisel 8, 13 , Dagmar Iber 3, 5, 13, ✱ , Erik van Nimwegen 2, 3, 13, ✱ and Verdon Taylor 1, 13, 14, ✱

Affiliations:

  • 1 Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
  • 2 Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland.
  • 3 Swiss Institute of Bioinformatics (SIB), Mattenstrasse 26, CH-4058 Basel, Switzerland.
  • 4 Eli and Edythe Broad Center of Regeneration Medicine and Stem cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, California-94143.
  • 5 Weill Institute for Neuroscience, San Francisco, 4th St, California-94158.
  • 6 Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California-94143.
  • 7 Computational Biology Group, D-BSSE, ETH Zürich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
  • 8 Department of Biosystems Science and Engineering, ETH Zürich, CH-4058 Basel, Switzerland.
  • 9 Swiss Data Science Center, Turnerstrasse 1, CH-8092 Zürich, Switzerland.
  • 10 Scientific IT Services, ETH Zürich, Binzmühlestrasse 130, CH-8092 Zürich, Switzerland.
  • 11 Faculty of Medicine, University of Zürich, Zürich.
  • 12 These authors contributed equally.
  • 13 Senior author.
  • 14 Lead contact.

✱ Correspondence: tanzila.mukhtar ( at ) ucsf.edu (T.M), dagmar.iber ( at ) bsse.ethz.ch (D.I), erik.vannimwegen ( at ) unibas.ch (E.vN) verdon.taylor ( at ) unibas.ch (V.T)

The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs) and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time, and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP and NBN clusters, and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders.

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