Inside Clockwork of Embryonic Body Patterning

a fluorescence image of an iPSM tissue model

Figure 1: A fluorescence image of an induced presomitic mesoderm (iPSM) tissue model, where cells expressing the Hes7 gene-a key regulator of somite formation-are labeled green. Purple cells express a gene that serves as a marker for somite tissue. © 2026 RIKEN Center for Biosystems Dynamics Research

The architecture of the body is not encoded as a formal blueprint; rather, it's the tightly orchestrated activation and deactivation of genes that coordinate body development.

Many of these processes are not fully understood, but RIKEN researchers have made important headway toward reconstructing how critical building blocks within a vertebrate embryo take shape1.

Early in development, a subset of cells develops into parallel tracts of structures known as somites, which give rise to the backbone, ribs and muscles. Somite formation arises from the cyclic activity of a network of genes, many of which have been identified.

"The molecular steps that generate the synchronized oscillations that propagate like waves across the embryonic tissue were not fully understood," notes Ryoichiro Kageyama of the RIKEN Center for Biosystems Dynamics Research.

Dissecting this process has been difficult. The relevant fluctuations in gene activity happen quickly inside the embryo-a mechanism known as the segmentation clock-making it difficult to visualize and manipulate somite formation as it unfolds.

Now, Kageyama and his colleagues have solved this problem by taking advantage of recently developed technological tools1,2,3.

They engineered mouse stem cells to develop into 'induced presomitic mesoderm' (iPSM), which closely simulates the precursor embryonic tissue that normally gives rise to somites.

"These iPSM models retain the key features of the in vivo segmentation clock," says Kageyama. This allowed his team to characterize how a key oscillator gene known as Hes7 helps drive the formation of somites.

Hes7 shuts off genes further along the signaling pathway. Kageyama's team identified one particularly interesting target: Cdh2 encodes an adhesion protein that normally serves as the molecular glue bonding cells together. It thereby influences patterning and segmentation of embryonic tissues.

By manipulating gene expression in iPSM constructs and then visualizing the effects with live-cell microscopy, the team was able to show that Hes7-mediated control of Cdh2 directly affects the FGF signaling pathway that provides direct developmental instructions to the timing of cell maturation during somite segmentation (Fig. 1).

Furthermore, the abnormal Cdh2 activity that arises from perturbed Hes7 expression leads to irregularities in adhesion between cells, undermining the structural integrity of developing somites.

"This finding provides another molecular bridge between oscillatory gene expression and signaling pathways, revealing how temporal information is translated into spatial patterns during embryogenesis," says Kageyama.

As such, he sees this work as an important step toward his team's ultimate goal of building a comprehensive spatial and temporal reconstruction of how the formation of somites unfolds.

Picture of Ryoichiro Kageyama and his lab members

Ryoichiro Kageyama (seventh from left) and his team have found that Cdh2 regulates somitogenesis by supporting FGF signaling. © 2026 RIKEN

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