Signals and circuits that regulate developmental timing

PROJECT SUMMARY Deviations from the order or timing of developmental events often result in abnormalities. Understanding how such well-regulated process can remain plastic, that is, be able to flexibly change depending on the environment is an important question. Social signals exchanged by members of the same species constitute a prominent

class of environmental effects that can alter development. A representative example of such social effects is the observation that female mammals attain sexual maturity faster if exposed to adult males. We found that males of the classic model species C. elegans also excrete signals that hasten sexual maturation of the opposite sex.

Our preliminary studies revealed the following features of this process. (A) Developmental acceleration occurs late indicating that the onset of adulthood is specifically hastened. (B) Developmental acceleration involves faster progression of events in multiple cell lineages suggesting that it is systemic. (C) Developmental acceleration is

accompanied by appropriately accelerated organismal growth. (D) Males excrete small-molecule signals that belong to two distinct chemical classes. Either molecule alone can accelerate development implying redundancy. (E) Sensory neurons are required for acceleration, suggesting that they may detect the acceleration-inducing

pheromones. (F) In addition to causing accelerated growth and development, these pheromones also alter behaviors involved in obtaining food, presumably to provide additional resources to sustain faster development. These findings serve as a foundation for our research program that will pursue the following goals. (1) Taking

advantage of the unique strengths of C. elegans as a model system, delineate neuronal circuits required to accelerate development in response to pheromones. These circuits are expected to consist of multiple neurons that signal to each other via specific transmitters and receptors. Major impact of this work will be the identification

of ways in which the nervous system non-autonomously regulates organismal growth and development. The promise of this approach is the ability to alter the rate of development and growth by opto- and chemogenetic manipulation of specific neurons. (2) To identify components of signaling pathways that are required for

acceleration, particularly those that coordinate development and growth. (3) An unexpected theme emerging from our work is that regulation of developmental events and appropriate behaviors are coupled because both rely on the same neuronal circuits. We are using machine-vision to simultaneously monitor behavior,

development, and growth to test this hypothesis. Our quantitative and innovative approach bridges concepts and tools from several distinct fields. We aim to provide an undertesting of developmental processes enriched by considerations of social interactions that are emerging as a major contributor to inter-individual developmental

variation, including as possible causes of disease states.