Cited by 225Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationCongenital gastrointestinal and neural anomalies

Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn

Glasgow, Stacey M., Henke, R. Michael, MacDonald, Raymond J., Wright, Christopher V. E., Johnson, Jane E.·2005·Development

Abstract

Mutations in the human and mouse PTF1A/Ptf1a genes result in permanent diabetes mellitus and cerebellar agenesis. We show that Ptf1a is present in precursors to GABAergic neurons in spinal cord dorsal horn as well as the cerebellum. A null mutation in Ptf1a reveals its requirement for the dorsal horn GABAergic neurons. Specifically, Ptf1a is required for the generation of early-born (dI4, E10.5) and late-born (dILA, E12.5)dorsal interneuron populations identified by homeodomain factors Lhx1/5 and Pax2. Furthermore, in the absence of Ptf1a, the dI4 dorsal interneurons trans-fate to dI5 (Lmx1b+), and the dILA to dILB (Lmx1b+;Tlx3+). This mis-specification of neurons results in a complete loss of inhibitory GABAergic neurons and an increase in the excitatory glutamatergic neurons in the dorsal horn of the spinal cord by E16.5. Thus, Ptf1a function is essential for GABAergic over glutamatergic neuronal cell fates in the developing spinal cord, and provides an important genetic link between inhibitory and excitatory interneuron development.

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Crossref · 10.1242/dev.02167

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  • A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations.

    “A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations, which was unexpected though there have been reports of scattered dI4 Ptf1a-derived cells in the embryonic and perinatal ventral horn103,104, and the very small dI6 population is known to be ventrally located105–107.”

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Authors
Glasgow, S. M., Henke, R. M., MacDonald, R. J., Wright, C. V. E., & Johnson, J. E.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Vanderbilt University (US)
Venue
Development
Published
2005-12-15
Volume
132
Issue
24
Pages
5461-5469
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2030148675
Cited by
225
References
37
Citations by year
2026: 5 · 2025: 4 · 2024: 12 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 9 · 2018: 6 · 2017: 12 · 2016: 14 · 2015: 11 · 2014: 10 · 2013: 28 · 2012: 14
FWCI
3.31
Type
journal article
Language
en
Open access
closed
Locations
  • Development (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health (1r01hd037032-01)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK42502)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD37032)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
Keywords
Ptf1a, dorsal horn, GABAergic neurons, glutamatergic neurons, neuronal cell fate specification, dorsal interneurons, Lhx1, PAX2, Lmx1b, TLX3, cerebellar agenesis, diabetes mellitus
MeSH terms
Animals, Cell Differentiation, Cerebellum, gamma-Aminobutyric Acid, Interneurons, Mice, Mutant Strains, Mutation, Neurons, Transcription Factors, Homeodomain Proteins, Glutamic Acid, Cell Lineage, Posterior Horn Cells, Mice, PAX2 Transcription Factor

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