The Role of PRDM12 in Nociceptor Development from Embryogenesis to Adulthood

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About this seminar:
Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause Congenital Insensitivity to Pain (CIP) due to failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue- and temporal-specific knockout mouse models to test the function of Prdm12 during development and in adulthood. We find that constitutive loss of Prdm12 causes deficiencies in proliferation during sensory neurogenesis. We also demonstrate that conditional knockout from dorsal root ganglia (DRGs) during embryogenesis causes defects in nociception. In contrast, we find that in adult DRGs, Prdm12 is dispensable for most pain sensation and injury-induced hypersensitivity. Using transcriptomic analysis, we found mostly unique changes in adult Prdm12 knockout DRGs compared to embryonic knockout, and that PRDM12 is likely a transcriptional activator in the adult. Overall, we find that the function of PRDM12 changes over developmental time.

Contributors

Helen Lai, PhD

Helen Lai, PhD, earned a BA in chemistry at Cornell University and a PhD in biophysics at the University of California, San Francisco, where she worked with Lily Jan to investigate the structural mechanisms of voltage-gated potassium channels, which help to define the signaling characteristics of neurons. As a postdoctoral fellow in Jane Johnson’s lab at The University of Texas Southwestern Medical Center, she studied tran¬scriptional mechanisms of differentiation and cell type specification in spinal cord and cerebellar neurons. She was a Sara and Frank McKnight Fellow at UT Southwestern from 2012 to 2015, when she became an assistant professor. Her lab is interested in understanding how somatosensory systems develop and are wired with a focus on proprioception and pain. In particular, her lab is interested in the genetic variation underlying pain sensation. Her work in this area was supported by a 2018 Rita Allen Foundation Fellowship.
Patrik Ernfors, PhD

Patrik Ernfors, PhD, received his PhD in molecular neurobiology in 1991 at Karolinska Institutet, under supervision of Professor Håkan Persson. After postdoctoral studies with Professor Rudolf Jaenisch at the Whitehead Institute for Biomedical Research in Boston, Dr. Ernfors returned to Sweden as a member of the junior faculty at Karolinska Institutet in 1994. He became Professor of Tissue Biology at the Karolinska Institutet in 1999. Among many academic functions, Dr. Ernfors has served as head of the Department of Medical Biochemistry and Biophysics, as a member of the Board of Research at Karolinska Institutet and as an editor at Science Advances. He is a member of the Royal Swedish Academy of Sciences and the Nobel Assembly at Karolinska Institutet.

DISCLOSURE: Nothing to disclose.

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Description

Contributors

Helen Lai, PhD

Patrik Ernfors, PhD