Multipotent radial glia sequentially deploy fate-restricted intermediate progenitors to diversify cortical interneurons
- 1Cold Spring Harbor Laboratory
Abstract
GABAergic interneurons deploy numerous inhibitory mechanisms that regulate cortical circuit operation, but the developmental programs that generate diverse interneuron types are not yet well understood. We carried out a comprehensive genetic fate mapping of the radial glial progenitors (RGs) and intermediate progenitors (IP) in the medial ganglionic eminence (MGE) in mice. We reveal that Nkx2.1+ RGs are multipotent and mediate two consecutive waves of neurogenesis, each sequentially generating different sets of interneuron types that laminate the neocortex in an inside-out-inside order. The first wave begins early and is restricted to the caudal MGE, has limited neurogenic window and capacity, and involves mostly apical IPs. The second wave begins later throughout the MGE, has an extended time course and large neurogenic capacity, and features a large set of fate-restricted basal IPs that amplify and diversify interneurons. Chandelier cells are generated toward the end of each wave and laminate in an outside-in order. Therefore, separate pools of multipotent RGs deploy temporal cohorts of IPs to sequentially generate diverse interneuron types.
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BibTeX
@misc{kelly2026multipotent,
title = {{Multipotent radial glia sequentially deploy fate-restricted intermediate progenitors to diversify cortical interneurons}},
author = {S. Kelly and R. Raudales and M. Moissidis and Z. J. Huang},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.1101/735019},
url = {https://www.biorxiv.org/content/10.1101/735019v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Multipotent radial glia sequentially deploy fate-restricted intermediate progenitors to diversify cortical interneurons
AU - S. Kelly
AU - R. Raudales
AU - M. Moissidis
AU - Z. J. Huang
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.1101/735019
UR - https://www.biorxiv.org/content/10.1101/735019v2
AB - GABAergic interneurons deploy numerous inhibitory mechanisms that regulate cortical circuit operation, but the developmental programs that generate diverse interneuron types are not yet well understood. We carried out a comprehensive genetic fate mapping of the radial glial progenitors (RGs) and intermediate progenitors (IP) in the medial ganglionic eminence (MGE) in mice. We reveal that Nkx2.1+ RGs are multipotent and mediate two consecutive waves of neurogenesis, each sequentially generating different sets of interneuron types that laminate the neocortex in an inside-out-inside order. The first wave begins early and is restricted to the caudal MGE, has limited neurogenic window and capacity, and involves mostly apical IPs. The second wave begins later throughout the MGE, has an extended time course and large neurogenic capacity, and features a large set of fate-restricted basal IPs that amplify and diversify interneurons. Chandelier cells are generated toward the end of each wave and laminate in an outside-in order. Therefore, separate pools of multipotent RGs deploy temporal cohorts of IPs to sequentially generate diverse interneuron types.
ER -