In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 9 ( 2022-9-6), p. e3001563-
Kurzfassung:
The development of stable specialized cell types in multicellular organisms relies on mechanisms controlling inductive intercellular signals and the competence of cells to respond to such signals. In developing cerebral cortex, progenitors generate only glutamatergic excitatory neurons despite being exposed to signals with the potential to initiate the production of other neuronal types, suggesting that their competence is limited. Here, we tested the hypothesis that this limitation is due to their expression of transcription factor Pax6. We used bulk and single-cell RNAseq to show that conditional cortex-specific Pax6 deletion from the onset of cortical neurogenesis allowed some progenitors to generate abnormal lineages resembling those normally found outside the cortex. Analysis of selected gene expression showed that the changes occurred in specific spatiotemporal patterns. We then compared the responses of control and Pax6-deleted cortical cells to in vivo and in vitro manipulations of extracellular signals. We found that Pax6 loss increased cortical progenitors’ competence to generate inappropriate lineages in response to extracellular factors normally present in developing cortex, including the morphogens Shh and Bmp4. Regional variation in the levels of these factors could explain spatiotemporal patterns of fate change following Pax6 deletion in vivo. We propose that Pax6’s main role in developing cortical cells is to minimize the risk of their development being derailed by the potential side effects of morphogens engaged contemporaneously in other essential functions.
Materialart:
Online-Ressource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001563
DOI:
10.1371/journal.pbio.3001563.g001
DOI:
10.1371/journal.pbio.3001563.g002
DOI:
10.1371/journal.pbio.3001563.g003
DOI:
10.1371/journal.pbio.3001563.g004
DOI:
10.1371/journal.pbio.3001563.g005
DOI:
10.1371/journal.pbio.3001563.g006
DOI:
10.1371/journal.pbio.3001563.g007
DOI:
10.1371/journal.pbio.3001563.g008
DOI:
10.1371/journal.pbio.3001563.g009
DOI:
10.1371/journal.pbio.3001563.s001
DOI:
10.1371/journal.pbio.3001563.s002
DOI:
10.1371/journal.pbio.3001563.s003
DOI:
10.1371/journal.pbio.3001563.s004
DOI:
10.1371/journal.pbio.3001563.s005
DOI:
10.1371/journal.pbio.3001563.s006
DOI:
10.1371/journal.pbio.3001563.s007
DOI:
10.1371/journal.pbio.3001563.s008
DOI:
10.1371/journal.pbio.3001563.s009
DOI:
10.1371/journal.pbio.3001563.s010
DOI:
10.1371/journal.pbio.3001563.s011
DOI:
10.1371/journal.pbio.3001563.s012
DOI:
10.1371/journal.pbio.3001563.s013
DOI:
10.1371/journal.pbio.3001563.s014
DOI:
10.1371/journal.pbio.3001563.s015
DOI:
10.1371/journal.pbio.3001563.s016
DOI:
10.1371/journal.pbio.3001563.s017
DOI:
10.1371/journal.pbio.3001563.s018
DOI:
10.1371/journal.pbio.3001563.s019
DOI:
10.1371/journal.pbio.3001563.s020
DOI:
10.1371/journal.pbio.3001563.s021
DOI:
10.1371/journal.pbio.3001563.s022
DOI:
10.1371/journal.pbio.3001563.s023
DOI:
10.1371/journal.pbio.3001563.s024
DOI:
10.1371/journal.pbio.3001563.s025
DOI:
10.1371/journal.pbio.3001563.s026
DOI:
10.1371/journal.pbio.3001563.s027
DOI:
10.1371/journal.pbio.3001563.s028
DOI:
10.1371/journal.pbio.3001563.s029
DOI:
10.1371/journal.pbio.3001563.s030
DOI:
10.1371/journal.pbio.3001563.s031
DOI:
10.1371/journal.pbio.3001563.s032
DOI:
10.1371/journal.pbio.3001563.s033
DOI:
10.1371/journal.pbio.3001563.s034
DOI:
10.1371/journal.pbio.3001563.s035
DOI:
10.1371/journal.pbio.3001563.r001
DOI:
10.1371/journal.pbio.3001563.r002
DOI:
10.1371/journal.pbio.3001563.r003
DOI:
10.1371/journal.pbio.3001563.r004
DOI:
10.1371/journal.pbio.3001563.r005
DOI:
10.1371/journal.pbio.3001563.r006
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2126773-X
Permalink