PUBLICATION
Progenitor neighborhoods function as transient niches to sustain olfactory neurogenesis
- Authors
- Rajan, S.G., Nacke, L.M., Lombardo, J.N., Manuchehrfar, F., Wong, K., Kanabar, P., Somodji, E.A., Garcia, J., Maienschein-Cline, M., Liang, J., Saxena, A.
- ID
- ZDB-PUB-250705-14
- Date
- 2025
- Source
- Stem Cell Reports : 102575102575 (Journal)
- Registered Authors
- Keywords
- cellular coordination, inter-organ communication, neural stem cells, neuronal differentiation, olfactory development, organogenesis, stochastic signaling, systems developmental biology, tissue patterning
- MeSH Terms
-
- Animals
- Brain-Derived Neurotrophic Factor/metabolism
- Cell Differentiation
- Neural Stem Cells*/cytology
- Neural Stem Cells*/metabolism
- Neurogenesis*
- Olfactory Mucosa*/cytology
- Olfactory Mucosa*/metabolism
- Olfactory Receptor Neurons/cytology
- Olfactory Receptor Neurons/metabolism
- Receptors, Notch/metabolism
- Signal Transduction
- Stem Cell Niche*
- Stem Cells*/cytology
- Stem Cells*/metabolism
- Tretinoin/metabolism
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 40614732 Full text @ Stem Cell Reports
Citation
Rajan, S.G., Nacke, L.M., Lombardo, J.N., Manuchehrfar, F., Wong, K., Kanabar, P., Somodji, E.A., Garcia, J., Maienschein-Cline, M., Liang, J., Saxena, A. (2025) Progenitor neighborhoods function as transient niches to sustain olfactory neurogenesis. Stem Cell Reports. :102575102575.
Abstract
Olfactory neurogenesis occurs throughout the lives of vertebrates, including in humans, and relies on the continuous differentiation and integration of neurons into a complex network. How progenitor cells convert fluctuations in cell-cell signaling into streamlined fate decisions over both space and time is poorly understood. Here, we track multicellular dynamics in the zebrafish olfactory epithelium, undertake targeted perturbations, and find that neurogenesis is driven by mutual antagonism between Notch signaling and insulinoma-associated 1a (Insm1a) that is responsive to inter-organ retinoic acid signaling. Single-cell analysis reveals that olfactory neurons emerge from transient groups of cells termed cellular neighborhoods. Stochastic modeling shows that neighborhood self-assembly is maintained by a tightly regulated bistable toggle switch. Differentiating cells migrate apically in response to brain-derived neurotrophic factor (BDNF) to take up residence as mature sensory neurons. Cumulatively, these findings reveal how stochastic signaling networks spatiotemporally regulate a balance between progenitors and derivatives, driving sustained neurogenesis in an intricate organ system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping