In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 8 ( 2023-8-8), p. e3002237-
Abstract:
In vivo direct neuronal reprogramming relies on the implementation of an exogenous transcriptional program allowing to achieve conversion of a particular neuronal or glial cell type towards a new identity. The transcription factor (TF) Fezf2 is known for its role in neuronal subtype specification of deep-layer (DL) subcortical projection neurons. High ectopic Fezf2 expression in mice can convert both upper-layer (UL) and striatal projection neurons into a corticofugal fate, even if at low efficiency. In this study, we show that Fezf2 synergizes with the nuclear co-adaptor Lmo4 to further enhance reprogramming of UL cortical pyramidal neurons into DL corticofugal neurons, at both embryonic and early postnatal stages. Reprogrammed neurons express DL molecular markers and project toward subcerebral targets, including thalamus, cerebral peduncle (CP), and spinal cord (SC). We also show that co-expression of Fezf2 with the reprogramming factors Neurog2 and Bcl2 in early postnatal mouse glia promotes glia-to-neuron conversion with partial hallmarks of DL neurons and with Lmo4 promoting further morphological complexity. These data support a novel role for Lmo4 in synergizing with Fezf2 during direct lineage conversion in vivo .
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002237
DOI:
10.1371/journal.pbio.3002237.g001
DOI:
10.1371/journal.pbio.3002237.g002
DOI:
10.1371/journal.pbio.3002237.g003
DOI:
10.1371/journal.pbio.3002237.g004
DOI:
10.1371/journal.pbio.3002237.g005
DOI:
10.1371/journal.pbio.3002237.g006
DOI:
10.1371/journal.pbio.3002237.g007
DOI:
10.1371/journal.pbio.3002237.g008
DOI:
10.1371/journal.pbio.3002237.t001
DOI:
10.1371/journal.pbio.3002237.s001
DOI:
10.1371/journal.pbio.3002237.s002
DOI:
10.1371/journal.pbio.3002237.s003
DOI:
10.1371/journal.pbio.3002237.s004
DOI:
10.1371/journal.pbio.3002237.s005
DOI:
10.1371/journal.pbio.3002237.s006
DOI:
10.1371/journal.pbio.3002237.s007
DOI:
10.1371/journal.pbio.3002237.s008
DOI:
10.1371/journal.pbio.3002237.s009
DOI:
10.1371/journal.pbio.3002237.s010
DOI:
10.1371/journal.pbio.3002237.s011
DOI:
10.1371/journal.pbio.3002237.s012
DOI:
10.1371/journal.pbio.3002237.s013
DOI:
10.1371/journal.pbio.3002237.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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