Decoding the molecular commonality underlying lip hypertrophy in cichlids

In a recent study, researchers have discovered that the genes related on extracellular matrix (ECM) and the Wnt signaling pathway characterize the independently acquired lip hypertrophy in cichlids of East African Great Lakes. Through advanced omics-based experiments and comparative histological analyses, they found that hypertrophied lips of cichlids had a larger proteoglycan-rich layer. This study provides vital insights into the evolutionary biology of lip hypertrophy in cichlids of East African Great Lakes.

Cichlids, a diverse family of freshwater fishes, are well-documented for their remarkable evolutionary traits. Over the years, these fishes have acquired unique facial features such as diverse snouts and varying jaw morphologies. Several reports indicate that the ability to adapt to a new environment has been a key feature of their evolution.

The cichlid fishes, especially those within the three East African Great Lakes of Victoria, Malawi, and Tanganyika, have independently evolved to achieve hypertrophied lips. The enlarged lips in these cichlids, which are a result of adaptive parallel evolution, are beneficial for foraging and detecting prey by providing a larger area of taste receptors. While different genetic influences and environmental factors are attributed to cause lip hypertrophy, the underlying molecular mechanisms are yet to be discovered.

To shed light on lip hypertrophy in cichlid fishes, researchers from Institute of Science Tokyo (Science Tokyo), Japan, collaborated with researchers from the Tanzania Fisheries Research Institute (TAFIRI), Tanzania, and conducted an in-depth study by comparing the genetic profiles and molecular pathways of cichlids with hypertrophied lips to those with normal lips. The research team led by Associate Professor Masato Nikaido comprised graduate students Nagatoshi Machii and Ryo Hatashima, Researcher Mitsuto Aibara, Assistant Professors Tatsuya Niwa and Tatsuki Nagasawa, Professor Hideki Taguchi, and researchers from the TAFIRI. Their findings were published online in eLife on April 22, 2025.

Initially, the researchers investigated the histological differences between hypertrophied lips and normal lips of cichlids from Lake Victoria, Lake Malawi, and Lake Tanganyika. They observed a significantly larger proteoglycan-rich layer within the extracellular matrix (ECM) of hypertrophied lips of cichlids from all lakes.

In subsequent proteomics-based analyses, the researchers found that 133 proteins were upregulated while the expression of 5 proteins was downregulated in the hypertrophied lips. “Interestingly, the tip of hypertrophied lips contained high amounts of proteoglycans and their related proteins such as versican and periostin,” remarks Nikaido.

Driven by their findings, the research team conducted transcriptome analysis to reveal commonality of hypertrophied lips among the three East African Great Lakes. Notably, the expression pattern of ECM-related genes reflected differences in lip morphology (hypertrophied and normal), regardless of the genetic closeness. In other words, the researchers identified the gene set that characterizes the hypertrophied lip among the independently acquired in the three lakes.

To decipher the molecular machinery involved in lip hypertrophy, the scientists examined advanced transcriptome analysis of the different developmental stages of cichlids. The results showed that genes involved in the Wnt signaling pathway were highly expressed in cichlids with hypertrophied lips at both the juvenile and adult stages.

Elaborating on the importance of the present study, Nikaido states, “The same ECM-related genes implicated in lip hypertrophy—such as versican and periostin—are also known to play key roles in human fibrotic skin diseases like keloids. Therefore, our study not only advances the current understanding of evolutionary biology in cichlids but also offers insights into skin diseases affecting humans.”

Taken together, this study reveals a shared molecular mechanism underlying the parallel evolution of lip hypertrophy in East African cichlid fishes.

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About Institute of Science Tokyo (Science Tokyo)
Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”