Ancient Genes Repurposed: How Limbs Evolved Their Complexity
An international research team, led by Konstanz-based biologist Joost Woltering, has unveiled crucial insights into the evolution of complex limbs in modern organisms. Their groundbreaking findings, published in "Molecular Biology and Evolution," detail how ancient genes, originally involved in fish midline fins, were remarkably repurposed to establish the dorsal-ventral axis in vertebrate limbs, such as human hands.
This genetic repurposing sheds light on the intricate evolutionary journey that transformed simple fin structures into the diverse and complex limbs we see today.
From Fins to Limbs: A 500-Million-Year Transformation
Approximately 500 million years ago, a pivotal genetic event occurred: the program for fish midline fins was duplicated and activated on the flanks of aquatic ancestors. This led to the development of the first paired fins. These paired fins continued to evolve, eventually giving rise to the paired limbs of vertebrates, including our arms and legs, around 350 million years ago.
Intriguing genetic similarities persist between fish midline fins and human limbs. For instance, the same genetic signals responsible for specifying a fish's back fin can also be found in human hands, where they dictate the development of the thumb and pinky finger. However, ancient midline fins, like those observed in sharks, exhibit identical left and right sides, notably lacking the dorsal-ventral (back-of-hand/palm) differentiation characteristic of vertebrate limbs.
Lmx1b: The Architect of Hand Shape
The Lmx1b gene plays a critical role in shaping hands during embryonic development. Cells where this gene is active differentiate into the back of the hand (dorsal side), while inactive cells form the palm (ventral side). The research team meticulously studied Lmx1b activation across various fish species, ranging from cichlids to sharks.
Their research revealed a significant difference in Lmx1b activation patterns, indicating a functional shift over evolutionary time.
In paired fins, direct precursors to our limbs, the gene is active on the dorsal surface, mirroring its function in human hands. Contrastingly, in midline fins, Lmx1b is activated towards the rear of the fin. This suggests that while Lmx1b was present in ancient fins, its original function was distinct and unrelated to the dorsal-ventral distinction.
Rewiring the Genetic Switches
The functional shift of Lmx1b from its ancestral role to defining the dorsal-ventral axis involved profound changes in its regulatory mechanisms. In paired fins, Lmx1b activity is primarily triggered by Wnt signaling. However, in ancient midline fins, Hedgehog signaling was the activating mechanism.
When Wnt signaling was experimentally deactivated in fish embryos, Lmx1b activity vanished in paired lateral fins but remained intact in midline fins. This crucial finding indicates that new regulatory switches evolved, effectively allowing for the gene's repurposing to serve a new function in limb development.
Lmx1b's Original Role: Guiding Neurons
Beyond its modern role in defining the dorsal-ventral axis in limbs, the researchers also successfully identified the ancestral function of Lmx1b in midline fins. They discovered that Lmx1b activates receptor molecules that are essential for guiding motor neurons to their correct muscles during embryonic development. This precise neuronal wiring is fundamental for facilitating limb extension and flexion.
The findings strongly suggest that the original function of the Lmx1b signal in midline fins was to ensure the proper neuronal wiring of the posterior fin musculature.