During early development, the brain and skull grow in tandem, their coordinated expansion ensuring both protection and function. This intricate partnership reflects millions of years of co-evolution, yet the genetic instructions that orchestrate their synchronized formation—and the evolutionary steps that shaped them—have remained elusive.

A team at the Max Planck Institute for Evolutionary Biology, led by Markéta Kaucká, has now traced those instructions to the MN1 gene. Although MN1 is best known for its links to brain tumors and leukemia, the researchers discovered that its origins extend back hundreds of millions of years to primitive invertebrates. At the dawn of vertebrate evolution—when animals first developed complex brains and protective cranial bones—MN1 acquired a novel C-terminal exon, a modification that proved essential for its later roles in vertebrate development.

By examining zebrafish and mouse embryos, the investigators demonstrated that MN1 is required to pattern the embryonic brain and, in turn, direct the formation of cranial bones. Loss of MN1 disrupted brain segmentation, led to abnormal cranial nerve development, and produced skull defects reminiscent of human conditions such as cleft palate and neurodevelopmental delay. Further analysis revealed that MN1 regulates retinoic acid levels and the expression of Hox genes—key components of an ancient signaling network that maps the body’s head-to-tail blueprint.

Beyond illuminating how vertebrate brains and skulls evolved in sync, the study also sheds light on clinical observations in leukemia. Patients with elevated MN1 expression often fail to respond to retinoic acid therapy because MN1 accelerates the drug’s degradation, undermining its effectiveness. Moreover, the researchers noted that MN1 truncations and mutations underlie a spectrum of human disorders, including neurodevelopmental and craniofacial syndromes. Together, these findings reveal how the evolution of a single gene can integrate into deep-rooted molecular systems to drive both developmental innovation and disease.

Source: https://www.mpg.de/24824285/0603-limn-revealing-the-link-between-the-brain-and-skull-co-evolution-and-co-development-153345-x?c=2249