Genetic and Environmental Perturbations During Development

Research Summary

Patricia Jensen, Ph.D., leads the Developmental Neurobiology Group and holds a secondary appointment in the NIEHS Reproductive and Developmental Biology Laboratory.

Motivated by evidence that noradrenergic neurons are differentially susceptible to disease and vary in sensitivity to certain toxicants, the Developmental Neurobiology Group uses intersectional genetic strategies in mice to uncover the developmental and genetic factors that may define this phenotypic diversity. These investigations combine cellular, molecular, behavioral and physiological approaches to provide insight into how genetic and environmental perturbation of distinct noradrenergic neuron subtypes early in development result in increased susceptibility to cognitive and affective disorders later in life.

Brainstem noradrenergic neurons comprise a small population of cells that project to virtually all areas of the central nervous system. Through the release of norepinephrine, these neurons modulate functions as diverse as attention, emotion, appetite, memory, and response to stress. Interestingly, it has been observed that subpopulations of noradrenergic neurons are differentially susceptible to disease and certain environmental exposures. Given these observations, we suspect that the key to understanding noradrenergic system dysfunction will not be found by focusing on the system as a whole. Rather, this phenotypic complexity will only be understood by uncovering the developmental and genetic factors that define unique functional subtypes of noradrenergic neurons.

Major areas of research:

  • Mammalian brain development
  • Neurodevelopmental origins of anxiety and depression
  • Mouse models of neurodevelopmental disorders

Current projects:

  • Deconstructing the complex noradrenergic system: linking molecular differences to structure and function
  • Uncovering the role of norepinephrine in brain development and the long-term structural and behavioral consequences of altered norepinephrine signaling

Jensen received her Ph.D. in anatomy and neurobiology at The University of Tennessee Health Science Center in 2002, working in the laboratory of Dan Goldowitz, Ph.D. As a doctoral student, she focused on the cellular and molecular interactions underlying cerebellar morphogenesis. During her postdoctoral training in the laboratory of Tom Curran, Ph.D., at St. Jude Children’s Research Hospital, Jensen managed the high-throughput in situ hybridization screen as part of the GENSAT project. In 2005, she joined the laboratory of Susan Dymecki, M.D., Ph.D., at Harvard Medical School as a postdoctoral fellow where she carried out molecular and genetic studies focusing on the embryonic and molecular development of individual serotonergic (5-HT) neuron subtypes. Jensen was recruited to the NIEHS in 2009.