Biomedical subjects

Alexander Aulehla

Publications and source records attributed to Alexander Aulehla.

5 recordsLinked to original sources

PubMed2025

A noncanonical role of glycolytic metabolites controlling the timing of mouse embryo segmentation.

Studies on the impact of metabolism on cell fate decisions are seeing a renaissance. However, a key challenge remains to distinguish signaling functions of metabolism from its canonical bioenergetic and biosynthetic roles, which underlie cellular homeostasis. Here, we tackled this challenge using mouse embryonic axis segmentation as an experimental model. First, we found that energetically subminimal amounts of glucose can support ongoing segmentation clock activity, providing evidence that glycolysis exerts a signaling function. Using a dynamical systems approach based on entrainment, we identified fructose 1,6-bisphosphate (FBP) as the potential signaling metabolite. Functionally, we demonstrated that glycolytic flux/FBP control the segmentation clock period and Wnt signaling in an anticorrelated manner. Critically, we showed that the slow segmentation clock phenotype caused by elevated glycolysis is mediated by Wnt signaling rather than cellular bioenergetic and biosynthetic state. Combined, our results demonstrate a modular organization of metabolic functions, revealing a signaling module of glycolysis that can be decoupled from its canonical metabolic functions.

Animals↗

PubMed2006

On periodicity and directionality of somitogenesis.

It is currently thought that the mechanism underlying somitogenesis is linked to a molecular oscillator, the segmentation clock, and to gradients of signaling molecules within the paraxial mesoderm. Here, we review the current picture of this segmentation clock and gradients, and use this knowledge to critically ask: What is the basis for periodicity and directionality of somitogenesis?

Animals↗

PubMed2004

WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos.

Notch signaling in the presomitic mesoderm (psm) is critical for somite formation and patterning. Here, we show that WNT signals regulate transcription of the Notch ligand Dll1 in the tailbud and psm. LEF/TCF factors cooperate with TBX6 to activate transcription from the Dll1 promoter in vitro. Mutating either T or LEF/TCF sites in the Dll1 promoter abolishes reporter gene expression in vitro as well as in the tail bud and psm of transgenic embryos. Our results indicate that WNT activity, in synergy with TBX6, regulates Dll1 transcription and thereby controls Notch activity, somite formation, and patterning.

Animals↗

PubMed2004

Segmentation in vertebrates: clock and gradient finally joined.

The vertebral column is derived from somites formed by segmentation of presomitic mesoderm, a fundamental process of vertebrate embryogenesis. Models on the mechanism controlling this process date back some three to four decades. Access to understanding the molecular control of somitogenesis has been gained only recently by the discovery of molecular oscillators (segmentation clock) and gradients of signaling molecules, as predicted by early models. The Notch signaling pathway is linked to the oscillator and plays a decisive role in inter- and intrasomitic boundary formation. An Fgf8 signaling gradient is involved in somite size control. And the (canonical) Wnt signaling pathway, driven by Wnt3a, appears to integrate clock and gradient in a global mechanism controlling the segmentation process. In this review, we discuss recent advances in understanding the molecular mechanism controlling somitogenesis.

Animals↗

PubMed2003

Wnt3a plays a major role in the segmentation clock controlling somitogenesis.

The vertebral column derives from somites generated by segmentation of presomitic mesoderm (PSM). Somitogenesis involves a molecular oscillator, the segmentation clock, controlling periodic Notch signaling in the PSM. Here, we establish a novel link between Wnt/beta-catenin signaling and the segmentation clock. Axin2, a negative regulator of the Wnt pathway, is directly controlled by Wnt/beta-catenin and shows oscillating expression in the PSM, even when Notch signaling is impaired, alternating with Lfng expression. Moreover, Wnt3a is required for oscillating Notch signaling activity in the PSM. We propose that the segmentation clock is established by Wnt/beta-catenin signaling via a negative-feedback mechanism and that Wnt3a controls the segmentation process in vertebrates.

Animals↗