In the sprawling tapestry of life on Earth, animals represent a stunning evolutionary achievement: the transition from single-celled organisms to complex multicellular entities composed of trillions of cells. These cells, while genetically almost identical, differentiate into a vast array of tissues and organs, orchestrating functions ranging from digestion to sensory perception. Among these remarkable cellular structures lies a singular tissue type—the germline—responsible for producing sperm and eggs, thus ensuring the continuity of species. Yet despite this fundamental biological process, the evolution of multicellularity in animals remains shrouded in mystery. Recent cutting-edge research emerging from the University of Chicago is shedding new light on this profound transformation by revealing the molecular innovations that likely enabled the early ancestors of animals to evolve not just multicellularity but also the ability to form a germline.
At the heart of multicellularity is the ability of cells to adhere and communicate, to arrange themselves spatially and temporally in complex patterns. Scientists have long known that cell-cell adhesion proteins existed even before the dawn of animals, in single-celled ancestors. However, these proteins alone could not fully explain the leap toward organized multicellular assemblies. The new study pivots attention to an often overlooked aspect of cell biology: cytokinesis, the pivotal process by which one cell divides into two daughter cells. While cytokinesis orchestrates cell division in all life forms, this research reveals that animals evolved a more sophisticated regulatory network that not only positions cell division precisely but also enables cells to remain physically connected after division—a critical step toward forming multicellular tissues and the specialized germline.
This sophisticated mechanism centers on three proteins: Kif23, Cyk4, and Ect2. These proteins intricately bind to each other and the mitotic spindle, the structure responsible for segregating chromosomes during cell division. Their interaction governs exactly where the cleavage furrow forms, marking the site where the cell will physically divide. Notably, two of these proteins, Kif23 and Cyk4, combine to form a stable complex known as centralspindlin, a structure discovered by Michael Glotzer and colleagues more than twenty years ago. Centralspindlin is more than a rudimentary scaffold; it forms a molecular bridge connecting daughter cells during cytokinesis.
Within most animal tissues, this bridge is transient, severed to allow daughter cells to separate fully. However, in germline cells—the precursors to sperm and eggs—these intercellular bridges frequently persist, enabling germline cells to remain physically connected within syncytial networks. This connectivity is hypothesized to facilitate critical developmental processes such as chromosomal recombination and cell fate determination, which underpin both genetic diversity and the formation of gametes. Thus, the persistence of these stable bridges is not merely a cellular curiosity but a functional cornerstone of animal reproduction.
Seeking to understand the evolutionary origins of this mechanism, Glotzer’s team undertook a comprehensive computational approach, leveraging the wealth of genomic data now available for a broad spectrum of animal species as well as closely related unicellular organisms. Their analyses demonstrated that all animal lineages possess conserved versions of Kif23, Cyk4, and Ect2, showing remarkable sequence conservation in motifs essential for their interactions and functions. By harnessing the artificial intelligence-driven AlphaFold platform, developed by University of Chicago alumnus and Nobel Laureate John Jumper, the researchers predicted the three-dimensional structures and interaction interfaces of these proteins. This evidence fortified the conclusion that the molecular machinery of centralspindlin and its regulatory partner Ect2 has been highly conserved since the emergence of animals over 800 million years ago.
Intriguingly, despite the absence of centralspindlin strictly speaking in unicellular organisms, somewhat related proteins were identified in choanoflagellates—single-celled eukaryotes regarded as the closest living relatives of animals. AlphaFold modeling suggested that choanoflagellate homologs might form protein complexes reminiscent of centralspindlin, yet lacking the specific sites for Ect2 binding. These structural differences appear to correspond to functional distinctions: some choanoflagellates can form simple colonies via incomplete cytokinesis, hinting at an evolutionary stepping stone toward animal multicellularity. This suggests that early genetic innovations in these protein complexes may have enabled ancestral cells to halt cytokinesis at an intermediate stage, remaining connected and cooperating within a colony rather than completely separating.
Glotzer’s hypothesis is both elegant and profound: the evolution of centralspindlin and its regulation by Ect2 was a pivotal event that allowed cells to "choose" to stay connected rather than fully separate after division. This partial cytokinesis not only facilitated the emergence of multicellular tissues but also laid the groundwork for germline development, fostering the biological genesis of animals as we know them. The idea that a mutation—or a set of mutations—in these proteins could have obstructed complete cytokinesis resonates as a conceivable, even likely, genetic mechanism that sparked the explosion of animal life on our planet.
This view of animal evolution reassesses long-held assumptions, placing molecular machinery involved in cytokinesis at the forefront of life’s major transitions. It also elucidates how the germline, a defining characteristic of animals with its capacity to transmit genetic information across generations, could have physically and genetically emerged in tandem with multicellularity. The findings underscore the intricate linkages between cellular architecture, protein evolution, and large-scale biological organization.
The technological strides enabling this discovery merit note. Without the synthesis of extensive genomic databases and AI-based protein modeling, the identification of conserved interaction motifs and the prediction of complex protein assemblies would be far more challenging, if not impossible. This research elegantly illustrates how computational simulation and modeling have become indispensable in modern biology, enabling scientists to peer back hundreds of millions of years through the molecular fossils encoded within genomes.
Moreover, the study provokes deeper thinking about incomplete cytokinesis as a versatile evolutionary strategy. The formation of stable intercellular bridges might not merely facilitate germline cohesion; it could represent a general principle by which early multicellular organisms orchestrated division, differentiation, and tissue organization. Such bridges could promote cell synchronization, sharing of cytoplasmic factors, and coordinated development, providing selective advantages that spurred further complexity.
Looking ahead, the evolutionary narrative outlined by Glotzer and colleagues invites experimental exploration to validate how variations in centralspindlin-Ect2 interactions modulate cytokinesis outcomes. It also offers a molecular framework for studying diseases linked to cytokinesis defects, including certain cancers and developmental disorders. Understanding the molecular logic that allowed cells to remain connected may reveal bioengineering strategies to manipulate cell adhesion and division in regenerative medicine and synthetic biology.
One cannot help but marvel at the fact that a mutation disrupting the assembly of centralspindlin—initially discovered more than 25 years ago through genetic experiments—has turned out to be a cornerstone event underpinning animal evolution. The confluence of ancient proteins, sophisticated modern tools, and evolutionary insight has produced a narrative as awe-inspiring as any chapter in the story of life.
In sum, this groundbreaking research reveals that the emergence of animal multicellularity and the germline was not a diffuse event but rather a molecular revolution centered around centralspindlin and its regulatory partner Ect2. Evolution harnessed a pre-existing, albeit simpler, cytokinesis toolkit in unicellular ancestors, refined it, and repurposed it to enable cells to remain interconnected through incomplete cytokinesis. This innovation underpinned the rise of organized tissues and the special reproductive lineage essential for animal life. The study fundamentally changes how we perceive the evolutionary steps from single cells to the complex creatures populating our planet today.
Subject of Research: Cells
Article Title: A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa
News Publication Date: 17-Jun-2025
References: Glotzer M. et al., "A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa," Current Biology, 2025.
Keywords: multicellularity, cytokinesis, centralspindlin, Ect2, germline, cell division, molecular evolution, Metazoa, protein complexes, AlphaFold, choanoflagellates, cell biology
