Investigating lineage decisions and migration mechanisms of cone photoreceptors in the developing zebrafish retina

• Applicant: Professor Dr. Alf Honigmann, since 1/2020
• Subject Area: Developmental Neurobiology ; Developmental Biology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413253148

• Final Report Year: 2024

Final Report Abstract

The implementation of this grant proposal resulted in a better understanding of lineage decisions in retinal morphogenesis (part 1) and non-canonical neuronal migration phenomena (part 2). Part 1. Overall, this part of the project contributed to the understanding of possibilities in lineage decisions in the retina and revealed different degrees of flexibility for different types of fate decisions. Studies like ours, combining live imaging with theoretical modelling, are important to understand the temporal dynamics of fate decisions that produce an organ of the correct size, cellular proportions and connectivity and will allow to reveal core principles of reproducible brain formation. Part 2. The main finding of this part of the project was that photoreceptors, undergo an intriguing bidirectional migration mode that is reminiscent of somal translocation in basal and apical direction. Interestingly, depending on direction, different cytoskeletal machineries are employed: microtubules drive cell bodies towards basal and actomyosin towards apical positions. Even more interestingly, we find that the bidirectional migration does not lead to a net displacement of cells, as photoreceptors return to the place where they were born and later fulfil their function. Instead, this counterintuitive migration phenomenon directly serves to coordinate growth and lamination in the developing retina. Precisely, it allows progenitor cells to still undergo apical divisions which are important for correct tissue maturation, while photoreceptors are temporarily moved out of the way. Thus, this study sets a new standard for the study of lamination phenomena taking cell and tissue wide components into account.

Publications

• Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway. eLife, 9.
  Nerli, Elisa; Rocha-Martins, Mauricio & Norden, Caren
  
• Stochasticity and determinism in cell fate decisions. Development, 147(14).
  Zechner, Christoph; Nerli, Elisa & Norden, Caren
  
• Deterministic and probabilistic fate decisions co‐exist in a single retinal lineage. The EMBO Journal, 42(14).
  Nerli, Elisa; Kretzschmar, Jenny; Bianucci, Tommaso; Rocha‐Martins, Mauricio; Zechner, Christoph & Norden, Caren
  
• Neuronal migration prevents spatial competition in retinal morphogenesis. Nature, 620(7974), 615-624.
  Rocha-Martins, Mauricio; Nerli, Elisa; Kretzschmar, Jenny; Weigert, Martin; Icha, Jaroslav; Myers, Eugene W. & Norden, Caren