Gene Regulation and the Origin of New Cell Types

The specialization of somatic cell types for unique functions is arguably the most important driver of physiological
complexity in animals. Key innovations in subcellular structure, including the development of a specialized
secretory vesicle, increased the evolvability of cells and provided new opportunities for cellular innovation during
the diversification of animals. For example, the emergence of cells with the capacity to secrete gel-forming mucus
enabled segregation of internal and external tissue compartments facilitating the evolution of organ systems.
Despite the value of novel cell function as a source for the evolution of animal complexity, the genomic
mechanisms promoting the origin and diversification of new cell types remain poorly understood. Recent
advances in sequencing technologies have provided a window into the genomic and transcriptomic environments
of numerous cell types from diverse organisms. While these studies have hypothesized roles for both newly
evolved genes and newly constructed regulatory relationships as critical elements of cell identity, understanding
how new genes get wired into gene regulatory networks (GRNs) to drive the origin of new cell types
remains a key gap in our knowledge of animal development. One challenge limiting progress in this area is
that it is still not feasible to manipulate gene expression in many animal models, hampering our ability to translate
observations of gene expression into functional relationships. A powerful system for modeling GRN evolution
must have a novel trait with a measurable phenotype, an identified network of genes controlling the trait, and a
genetically tractable organism for experimental testing. The novel and diverse seminal fluid proteins of
Drosophila fit all these characteristics and studies in this system have revealed how novel effector genes can
rapidly acquire essential functions affecting both physiology and behavior. Cnidocytes – the explosive, venom-
rich piercing cells that give jellyfish their sting – offer many of the same benefits as Drosophila for
modeling GRN evolution. Unique in both form and function, cnidocytes comprise a diverse lineage of cell types
found only in cnidarians (corals, sea anemones, and jellyfish). Many of the regulatory genes necessary for
cnidocyte development are already known to be novel and unique to this cell type, providing an unparalleled
opportunity to study how new transcription factors become indispensable for the origin of new cell types. The
proposed research will achieve three goals; it will: (1) construct the network of genes controlling the unique
morphologies of the four types of cnidocyte in the sea anemone Nematostella vectensis, (2) reveal the step-wise
assembly of a unique GRN subcircuit through comparisons of closely related cnidarians, and (3) develop a
technique for redirecting cells to acquire novel secretory functions. By constructing the GRN that promotes
morphogenesis in diverse cnidocyte types, we can pinpoint the genes necessary to drive autonomous
development of the piercing apparatus in new cell types. Thus, this research provides a framework for
adapting cnidocytes for other novel functions that could contribute to new delivery mechanisms for topical drugs.

Grant Number: 5R35GM147253-04
NIH Institute/Center: NIH
Principal Investigator: Leslie Babonis