The last decade has seen the discovery and functional annotation of numerous high-confidence autism spectrum disorder (ASD) risk genes. In the time since, much effort has been dedicated to understanding how these genes impact nervous system development. A consensus has emerged that many genes implicated in ASD susceptibility impact early steps in neurodevelopment, such as the timing and execution of neural differentiation, migration, and synaptogenesis, with such cellular phenotypes thought to be rooted in altered epigenomic and transcriptomic landscapes.
In parallel, SFARI has invested in efforts to characterize the impact of ASD risk gene mutation on the neural circuits underlying ASD-relevant phenotypes, with notable advances made in understanding the contribution of peripheral and central circuits to ASD-related sensory atypicalities, motor phenotypes, sleep disruptions, and social behavioral deficits, among other phenotypes.
While progress has been made toward understanding early development and mature functional outcomes in isolation, studies causally linking disruptions of early neurodevelopment to alterations in ASD-relevant neural circuits remain rare. The objective of this RFA is to bridge this critical gap in our understanding of how developmental events impact later processes of circuit formation and function in ASD.
We envision that this RFA will bring together scientists of diverse expertise, such as developmental neurobiologists and circuit neuroscientists, to collaboratively conduct thorough characterizations of how early developmental events result in alterations to ASD-relevant neural circuitry in carefully chosen models.
