Lens Placode Modulates Extracellular Matrix Formation During Early Eye Development
Posted on: 28 February 2024 , updated on: 29 February 2024
Preprint posted on 1 December 2023
Article now published in Differentiation at http://dx.doi.org/10.1016/j.diff.2024.100792
Lens placodes to put the journey of cells under a lens from the perspective of the extracellular matrix (ECM)
Selected by Bhaval Parmar
Categories: biochemistry, cell biology, developmental biology
Background
Embryonic development is a highly intricate process that involves a lot of different cellular activities. While the interactions between cells have been extensively studied in this context, the interaction of cells with the extracellular matrix (ECM) and the regulation of the ECM structure during embryonic development remain relatively unexplored. The ECM plays a vital role in the morphogenesis of epithelial tissue, forming structures such as the optic vesicles, otic vesicles, and heart tube. Any variations in the ECM can cause changes in the cellular behavior of epithelial cells. The lens is one such organ that is affected by these changes during embryonic development.
The lens in vertebrate eyes develops from a single-layer epithelial cells that later thicken and change shape. The surrounding ECM also undergoes changes that aid in growth. The ECM components are crucial in modulating cellular behaviour during embryonic development. The two primary components of the ECM are laminin α1 and fibronectin, along with glycoproteins. BMP signaling regulates the levels of laminin α1 and fibronectin, and during lens placode development, the composition of the ECM changes as the levels of these two components vary. The authors of this study found that the expression of TIMP, a protein that regulates the activity of MMPs, is also under the control of BMP signaling in the developing optic region. The change in the ECM leads to the differentiation of pre-placodal to placodal cells, which ultimately leads to the formation of the lens. This study shows a correlation between BMP signaling and the ECM components that regulate lens placode formation.
Key contributions
The authors of this preprint were able to identify changes in ECM components during lens placode formation. The observed ECM modulation was restricted to the placodes only and it was regulated by BMP signaling. Along with that, scRNA data for various ECM components such as collagens, elastin and fibronectin were checked in the lens placodal region of the chick and mice embryo. Overall, the key findings from this study can be summarised as follows:
- The distribution of fibronectin and laminin 1 in the lens placode of a chick embryo indicated that fibronectin is expressed in the non-placodal region along with laminin 1. However, laminin 1 was weakly expressed in the placodal region of the developing embryo.
- The ECM located in the optic region is regulated by BMP signaling. When tBMPr was used to inhibit BMP signaling, it hindered the thickening of the lens placode. However, in the absence of BMP signaling, the lens placodal cells remained in cuboidal morphology while the optic vesicle developed normally.
- Lens placodes modulate the ECM by regulating gelatinase activity. In silico observations showed an increase in TIMP2 expression in the optic region during placode formation.
- The study showed a correlation between ECM proteins and BMP signaling, as well as metalloprotease activity. Inhibition of BMP signaling directly affected TIMP2 expression in the optic region.
Collectively, these efforts have shed light on the complex interactions between the extracellular matrix (ECM) and the development of the lens during embryonic stages. The relationship between BMP signaling and the variation in the levels of fibronectin and laminin 1 provides insight into the significance of the ECM in the process of organ development and morphogenesis.
Conclusion/Why I highlight this preprint
This preprint has provided me with a fresh outlook on the significance of the extracellular matrix in tissue morphogenesis and organ development. The key discoveries have been substantiated by single-cell RNA sequencing in two animal models. In essence, this extensive dataset intends to offer fundamental insights into ECM remodeling and the control of molecular signaling during organogenesis. As such, the research presented in this preprint holds immense relevance for the study of embryonic development and serves as a stepping stone toward comprehending congenital eye diseases.
Questions/Future directions
- In this study, the inhibition of BMP signaling was achieved through the inhibition of its receptor. However, several types of BMP ligands are involved in the remodelling of the ECM. Therefore, it is worth considering the possibility of inhibiting specific isoforms and observing the resulting outcomes.
- Is there an upstream regulator of BMP that controls the BMP expression pattern in the placodal region?
- What are the intermediate molecules that regulate BMP signaling and lead to changes in ECM components such as fibronectin and laminin?
- Does inhibiting the BMP receptor have any effect on the assembly of the cell’s cytoskeleton?
doi: https://doi.org/10.1242/prelights.36615
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