A Human Accelerated Region Drives Opposing Heterochronic Changes in Craniofacial and Limb Development
Many human developmental processes proceed over a prolonged timescale compared to other primates, a phenomenon known as heterochrony. Human accelerated regions (HARs), which encode transcriptional enhancers with human-specific activity, have been implicated in the evolution of novel human traits. However, their contributions to changes in developmental timing remain unknown. Using single-nucleus…
Human developmental processes unfold more slowly in humans than in other primates, a condition known as heterochrony. Certain human-specific gene regulatory regions, called Human Accelerated Regions (HARs), have been linked to the emergence of distinctively human features. However, the role of these HARs in altering developmental timing has been unclear.
A study using a mouse model genetically modified to express the HAR HACNS1 has revealed that HACNS1 induces opposing changes in the speed of craniofacial and limb development.
The research, conducted through single-nucleus RNA sequencing and developmental trajectory analyses, demonstrated that HACNS1 slows down chondrocyte differentiation and the expression of cartilage and skeletal maturation genes in pharyngeal arches. Conversely, in limb buds, HACNS1 hastens chondrogenesis and boosts the early expression of differentiation-associated genes.
These transcriptomic shifts are reflected in the morphology of SOX9-expressing pre-cartilaginous domains, which become more dispersed in pharyngeal arches but condensed in limb buds.
Further analysis of gene regulatory networks suggests that HACNS1's heterochronic effects are primarily due to alterations in the expression of its target gene Gbx2. This, in turn, triggers downstream changes in the regulatory networks through which Gbx2 plays a role. The study's conclusions indicate that a single human-specific gene regulatory change can significantly modify developmental timing, offering a potential mechanism for how unique genetic modifications in humans have reshaped inherited developmental pathways.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
