PUBLICATION
Zebrafish anterior segment mesenchyme progenitors are defined by function of tfap2a but not sox10
- Authors
- Vöcking, O., Van Der Meulen, K., Patel, M.K., Famulski, J.K.
- ID
- ZDB-PUB-221224-39
- Date
- 2022
- Source
- Differentiation; research in biological diversity 130: 324232-42 (Journal)
- Registered Authors
- Famulski, Jakub
- Keywords
- Anterior segment, Cornea, Neural crest, Periocular mesenchyme, Zebrafish, tfap2
- MeSH Terms
-
- Animals
- Forkhead Transcription Factors/genetics
- Gene Expression Regulation, Developmental
- In Situ Hybridization, Fluorescence
- Mesoderm/metabolism
- Neural Crest/metabolism
- Transcription Factor AP-2/genetics
- Transcription Factor AP-2/metabolism
- Transcription Factors/genetics
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- PubMed
- 36563566 Full text @ Differentiation
Citation
Vöcking, O., Van Der Meulen, K., Patel, M.K., Famulski, J.K. (2022) Zebrafish anterior segment mesenchyme progenitors are defined by function of tfap2a but not sox10. Differentiation; research in biological diversity. 130:324232-42.
Abstract
The anterior segment is a critical component of the visual system. Developing independent of the retina, the AS relies partially on cranial neural crest cells (cNCC) as its earliest progenitors. The cNCCs are thought to first adopt a periocular mesenchyme (POM) fate and subsequently target to the AS upon formation of the rudimentary retina. AS targeted POM is termed anterior segment mesenchyme (ASM). However, it remains unknown when and how the switch from cNCC to POM or POM to ASM takes place. As such, we sought to visualize the timing of these transitions and identify the regulators of this process using the zebrafish embryo model. Using two color fluorescence in situ hybridization, we tracked cNCC and ASM target gene expression from 12 to 24hpf. In doing so, we identified a tfap2a and foxC1a co-expression at 16hpf, identifying the earliest ASM to arrive at the AS. Interestingly, expression of two other key regulators of NCC, foxD3 and sox10 was not associated with early ASM. Functional analysis of tfap2a, foxD3 and sox10 revealed that tfap2a and foxD3 are both critical regulators of ASM specification and AS formation while sox10 was dispensable for either specification or development of the AS. Using genetic knockout lines, we show that in the absence of tfap2a or foxD3 function ASM cells are not specified, and subsequently the AS is malformed. Conversely, sox10 genetic mutants or CRISPR Cas9 injected embryos displayed no defects in ASM specification, migration or the AS. Lastly, using transcriptomic analysis, we show that GFP + cNCCs derived from Tg [foxD3:GFP] and Tg [foxC1b:GFP] share expression profiles consistent with ASM development whereas cNCCs isolated from Tg [sox10:GFP] exhibit expression profiles associated with vasculogenesis, muscle function and pigmentation. Taken together, we propose that the earliest stage of anterior segment mesenchyme (ASM) specification in zebrafish is approximately 16hpf and involves tfap2a/foxC1a positive cNCCs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping