Aufklärung der Mechanismen zur Entstehung intermediärer Vorläuferzellen (IPs) während der kortikalen Entwicklung.

• Antragsteller: Dr. Froylan Calderon de Anda
• Fachliche Zuordnung: Entwicklungsneurobiologie
• Förderung: Förderung von 2017 bis 2022
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 392669675

• Erstellungsjahr: 2023

Zusammenfassung der Projektergebnisse

Rapid, diverse, and robust amplification is characteristic of EOMES-expressing tissue. EOMES is found during the formation of the embryonic head and cardiac mesoderm, but also in activated T cells, cancer, and inflamed tissue. The context of this EOMES-driven amplification is often ambivalent and elusive, and therefore the subject of controversy. We hypothesize that excitotoxicity leads to cell cycle promotion in a glycolytic context, where EOMES most effectively promotes fate-specific target genes. It is important to note that this hypothetical link between the occurrence of these EOMES+ systems through excitotoxicity has not yet been systematically investigated. In summary, we can already deduce critical markers on the “border” of physiological neurogenesis from our RT-PCR validated RNAseq analysis and morphological assays, whilst we want to complete the landscape by covering the translational level (mass spectrometry) and the epigenetic level (meATACseq) with the same aliquots from all experiments. By joining all these levels, an unbiased multi-omics analysis across the specific different cell populations analysed will provide the scientific community with a rich dataset that challenges old dogmata and opens new questions on corticogenesis. Moreover, by testing the influence of MIA during cortical development, we are uncovering the role of the environment in the expression of Tbr2 which shed light on the molecular events that support the formation of IPs.

Projektbezogene Publikationen (Auswahl)

• Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling. Molecular Psychiatry, 24(9), 1329-1350.
  Richter, Melanie; Murtaza, Nadeem; Scharrenberg, Robin; White, Sean H.; Johanns, Ole; Walker, Susan; Yuen, Ryan K. C.; Schwanke, Birgit; Bedürftig, Bianca; Henis, Melad; Scharf, Sarah; Kraus, Vanessa; Dörk, Ronja; Hellmann, Jakob; Lindenmaier, Zsuzsa; Ellegood, Jacob; Hartung, Henrike; Kwan, Vickie; Sedlacik, Jan ... & Calderon, de Anda Froylan
  
• Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood. Nature Microbiology, 3(10), 1161-1174.
  Stanelle-Bertram, Stephanie; Walendy-Gnirß, Kerstin; Speiseder, Thomas; Thiele, Swantje; Asante, Ivy Asantewaa; Dreier, Carola; Kouassi, Nancy Mounogou; Preuß, Annette; Pilnitz-Stolze, Gundula; Müller, Ursula; Thanisch, Stefanie; Richter, Melanie; Scharrenberg, Robin; Kraus, Vanessa; Dörk, Ronja; Schau, Lynn; Herder, Vanessa; Gerhauser, Ingo; Pfankuche, Vanessa Maria ... & Gabriel, Gülsah
  
• Maintenance of cell type-specific connectivity and circuit function requires Tao kinase. Nature Communications, 10(1).
  Tenedini, Federico Marcello; Sáez, González Maria; Hu, Chun; Pedersen, Lisa Hedegaard; Petruzzi, Mabel Matamala; Spitzweck, Bettina; Wang, Denan; Richter, Melanie; Petersen, Meike; Szpotowicz, Emanuela; Schweizer, Michaela; Sigrist, Stephan J.; Calderon, de Anda Froylan & Soba, Peter
  
• Radial somatic F‐actin organization affects growth cone dynamics during early neuronal development. EMBO reports, 20(12).
  Meka, Durga Praveen; Scharrenberg, Robin; Zhao, Bing; Kobler, Oliver; König, Theresa; Schaefer, Irina; Schwanke, Birgit; Klykov, Sergei; Richter, Melanie; Eggert, Dennis; Windhorst, Sabine; Dotti, Carlos G.; Kreutz, Michael R.; Mikhaylova, Marina & Calderon, de Anda Froylan
  
• Conserved Tao Kinase Activity Regulates Dendritic Arborization, Cytoskeletal Dynamics, and Sensory Function inDrosophila. The Journal of Neuroscience, 40(9), 1819-1833.
  Hu, Chun; Kanellopoulos, Alexandros K.; Richter, Melanie; Petersen, Meike; Konietzny, Anja; Tenedini, Federico M.; Hoyer, Nina; Cheng, Lin; Poon, Carole L.C.; Harvey, Kieran F.; Windhorst, Sabine; Parrish, Jay Z.; Mikhaylova, Marina; Bagni, Claudia; Calderon, de Anda Froylan & Soba, Peter
  
• Centrosome-dependent microtubule modifications set the conditions for axon formation. Cell Reports, 39(3), 110686.
  Meka, Durga Praveen; Kobler, Oliver; Hong, Shuai; Friedrich, Carina Meta; Wuesthoff, Souhaila; Henis, Melad; Schwanke, Birgit; Krisp, Christoph; Schmuelling, Nessa; Rueter, René; Ruecker, Tabitha; Betleja, Ewelina; Cheng, Tao; Mahjoub, Moe R.; Soba, Peter; Schlüter, Hartmut; Fornasiero, Eugenio F. & Calderon, de Anda Froylan
  
• Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies. Cell Reports, 41(8), 111678.
  Murtaza, Nadeem; Cheng, Annie A.; Brown, Chad O.; Meka, Durga Praveen; Hong, Shuai; Uy, Jarryll A.; El-Hajjar, Joelle; Pipko, Neta; Unda, Brianna K.; Schwanke, Birgit; Xing, Sansi; Thiruvahindrapuram, Bhooma; Engchuan, Worrawat; Trost, Brett; Deneault, Eric; Calderon, de Anda Froylan; Doble, Bradley W.; Ellis, James; Anagnostou, Evdokia ... & Singh, Karun K.
  
• Pum2 and TDP-43 refine area-specific cytoarchitecture post-mitotically and modulate translation of Sox5, Bcl11b, and Rorb mRNAs in developing mouse neocortex. eLife, 11.
  Harb, Kawssar; Richter, Melanie; Neelagandan, Nagammal; Magrinelli, Elia; Harfoush, Hend; Kuechler, Katrin; Henis, Melad; Hermanns-Borgmeyer, Irm; Calderon, de Anda Froylan & Duncan, Kent
  
• TAOK2 rescues autism-linked developmental deficits in a 16p11.2 microdeletion mouse model. Molecular Psychiatry, 27(11), 4707-4721.
  Scharrenberg, Robin; Richter, Melanie; Johanns, Ole; Meka, Durga Praveen; Rücker, Tabitha; Murtaza, Nadeem; Lindenmaier, Zsuzsa; Ellegood, Jacob; Naumann, Anne; Zhao, Bing; Schwanke, Birgit; Sedlacik, Jan; Fiehler, Jens; Hanganu-Opatz, Ileana L.; Lerch, Jason P.; Singh, Karun K. & de, Anda Froylan Calderon