Development
Author: Carla Campetella | Email: ccampetella@leloir.org.ar
Carla Campetella1°, Guillermo Lanuza1°
1° Fundación Instituto Leloir
During embryonic development, some spinal cord progenitors are still capable of producing neurons after the neurogenic-to-gliogenic switch. We have previously demonstrated that late neurogenesis exclusively generates Pkd2l1+ CerebroSpinal Fluid-contacting Neurons (CSF-cNs), a discrete sensory neuron type in the ependymal area. Here we show that Pkd2l1+ neurons originate from two Ascl1-expressing progenitor pools (p2/pOL and p3 domains) to produce four distinct subtypes: Lateral, Ventral, Distal-Ventral and Distal-Lateral. Our experiments show that neurons of each cluster have a specific embryonic origin, migration, final settlement and variations of a common developmental program. Using mouse molecular genetics, we found that Pkd2l1+ Lateral, Distal-Ventral and Distal-Lateral derive from p2/pOL cells and require Pax6 for their differentiation. The proneural factor Ascl1 determines CSF-cN production, but surprisingly the delaminating Distal-Ventral cells are still present in Ascl1-KO. Finally, we precisely defined the temporal activation of Gata3/2 transcription factors along postmitotic specialization. To dig deeper into their role in the specification program we generated mice with varying combinations of Gata3/2 conditional or null alleles, and found that each cluster has differing requirements for gene dosage of Gata factors. All in all, we have dissected the role of Ascl1, Pax6 and Gata3/2 throughout the differentiation pathway of late-born spinal Pkd2l1+ neurons.