Title | Misexpression of ptf1a in cortical pyramidal cells in vivo promotes an inhibitory peptidergic identity. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Russ JB, Borromeo MD, Kollipara RK, Bommareddy PK, Johnson JE, Kaltschmidt JA |
Journal | J Neurosci |
Volume | 35 |
Issue | 15 |
Pagination | 6028-37 |
Date Published | 2015 Apr 15 |
ISSN | 1529-2401 |
Keywords | Animals, Animals, Newborn, Cerebral Cortex, Computational Biology, Electroporation, Embryo, Mammalian, Eye Proteins, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Homeodomain Proteins, Ki-67 Antigen, Mice, Mice, Transgenic, Nerve Tissue Proteins, Paired Box Transcription Factors, PAX6 Transcription Factor, Peptides, Pyramidal Cells, Repressor Proteins, Statistics, Nonparametric, Transcription Factors, Transcriptome, Tubulin |
Abstract | The intracellular transcriptional milieu wields considerable influence over the induction of neuronal identity. The transcription factor Ptf1a has been proposed to act as an identity "switch" between developmentally related precursors in the spinal cord (Glasgow et al., 2005; Huang et al., 2008), retina (Fujitani et al., 2006; Dullin et al., 2007; Nakhai et al., 2007; Lelièvre et al., 2011), and cerebellum (Hoshino et al., 2005; Pascual et al., 2007; Yamada et al., 2014), where it promotes an inhibitory over an excitatory neuronal identity. In this study, we investigate the potency of Ptf1a to cell autonomously confer a specific neuronal identity outside of its endogenous environment, using mouse in utero electroporation and a conditional genetic strategy to misexpress Ptf1a exclusively in developing cortical pyramidal cells. Transcriptome profiling of Ptf1a-misexpressing cells using RNA-seq reveals that Ptf1a significantly alters pyramidal cell gene expression, upregulating numerous Ptf1a-dependent inhibitory interneuron markers and ultimately generating a gene expression profile that resembles the transcriptomes of both Ptf1a-expressing spinal interneurons and endogenous cortical interneurons. Using RNA-seq and in situ hybridization analyses, we also show that Ptf1a induces expression of the peptidergic neurotransmitter nociceptin, while minimally affecting the expression of genes linked to other neurotransmitter systems. Moreover, Ptf1a alters neuronal morphology, inducing the radial redistribution and branching of neurites in cortical pyramidal cells. Thus Ptf1a is sufficient, even in a dramatically different neuronal precursor, to cell autonomously promote characteristics of an inhibitory peptidergic identity, providing the first example of a single transcription factor that can direct an inhibitory peptidergic fate. |
DOI | 10.1523/JNEUROSCI.3821-14.2015 |
Alternate Journal | J. Neurosci. |
PubMed ID | 25878276 |
PubMed Central ID | PMC4397601 |
Grant List | R01 HD037932 / HD / NICHD NIH HHS / United States R01 NS083998 / NS / NINDS NIH HHS / United States T32GM007739 / GM / NIGMS NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm