@article{adb0230d6c9d48ea8bc1246e3e9ca629,
title = "Positive autofeedback regulation of Ptf1a transcription generates the levels of PTF1A required to generate itch circuit neurons",
abstract = "Peripheral somatosensory input is modulated in the dorsal spinal cord by a network of excitatory and inhibitory interneurons. PTF1A is a transcription factor essential in dorsal neural tube progenitors for specification of these inhibitory neurons. Thus, mechanisms regulating Ptf1a expression are key for generating neuronal circuits underlying somatosensory behaviors. Mutations targeted to distinct cis-regulatory elements for Ptf1a in mice, tested the in vivo contribution of each element individually and in combination. Mutations in an autoregulatory enhancer resulted in reduced levels of PTF1A, and reduced numbers of specific dorsal spinal cord inhibitory neurons, particularly those expressing Pdyn and Gal. Although these mutants survive postnatally, at ∼3-5 wk they elicit a severe scratching phenotype. Behaviorally, the mutants have increased sensitivity to itch, but acute sensitivity to other sensory stimuli such as mechanical or thermal pain is unaffected. We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits.",
keywords = "Autoregulation, BHLH transcription factor, Cell fate specification, Inhibitory neuron, Itch, Neuronal identity, Somatosensory, Spinal cord development, Transcriptional control",
author = "Bishakha Mona and Juan Villarreal and Savage, {Trisha K.} and Kollipara, {Rahul K.} and Boisvert, {Brooke E.} and Johnson, {Jane E.}",
note = "Funding Information: We acknowledge the many hours of helpful discussions with Dr. H. Lai, and critical reading of the manuscript by Dr. H. Lai and Dr. S. Ross. We are grateful for the excellent transgenic mouse services provided by the University of Texas Southwestern Transgenic Core (Dr. R. Hammer, Director), and the access to microscopy in the Neuroscience Microscopy Facility supported by the University of Texas Southwestern Neuroscience Department and the Peter O'Donnell Jr. Brain Institute. We acknowledge the generous gifts from Dr. T. Muller and Dr. C. Birchmeier (TLX1/3 and LMX1B antibodies), as well as Dr. S. Ross (BHLHB5 antibodies). B.E.B. was a University of Texas Southwestern SURF-Stem Cell student supported by the Hamon Center for Regenerative Science and Medicine. This work was supported by the National Institutes of Health R01 HD037932 and R37 HD091856 to J.E.J. Funding Information: We acknowledge the many hours of helpful discussions with Dr. H. Lai, and critical reading of the manuscript by Dr. H. Lai and Dr. S. Ross. We are grateful for the excellent transgenic mouse services provided by the University of Texas Southwestern Transgenic Core (Dr. R. Hammer, Director), and the access to microscopy in the Neuroscience Microscopy Facility supported by the University of Texas Southwestern Neuroscience Department and the Peter O{\textquoteright}Donnell Jr. Brain Institute. We acknowledge the generous gifts from Dr. T. Muller and Dr. C. Birch-meier (TLX1/3 and LMX1B antibodies), as well as Dr. S. Ross (BHLHB5 antibodies). B.E.B. was a University of Texas South-western SURF-Stem Cell student supported by the Hamon Center for Regenerative Science and Medicine. This work was supported by the National Institutes of Health R01 HD037932 and R37 HD091856 to J.E.J. Publisher Copyright: {\textcopyright} 2020 Mona et al.",
year = "2020",
month = may,
day = "1",
doi = "10.1101/gad.332577.119",
language = "English (US)",
volume = "34",
pages = "621--636",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "9-10",
}