Lrig1 regulates cell fate specification of glutamatergic neurons via FGF-driven Jak2/Stat3 signaling in cortical progenitors.

De Vincenti, Ana Paula; Bonafina, Antonela; Ledda, Fernanda; Paratcha, Gustavo

doi:10.1242/dev.202879

Article (Scientific journals)

Lrig1 regulates cell fate specification of glutamatergic neurons via FGF-driven Jak2/Stat3 signaling in cortical progenitors.

De Vincenti, Ana Paula; Bonafina, Antonela; Ledda, Fernanda et al.

2024 • In Development, 151 (17)

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https://hdl.handle.net/2268/330704

DOI
10.1242/dev.202879

PubMed
39250533

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Keywords :

Cortical progenitors; Embryonic cortical development; Glutamatergic neurogenesis; IL6/Jak2/Stat3 pathway; Lrig1; STAT3 Transcription Factor; Janus Kinase 2; Membrane Glycoproteins; Lrig1 protein, mouse; Stat3 protein, mouse; Jak2 protein, mouse; Fibroblast Growth Factors; Nerve Tissue Proteins; Animals; Mice; Cell Proliferation; Cerebral Cortex/metabolism; Cerebral Cortex/cytology; Cerebral Cortex/embryology; Cell Differentiation; Fibroblast Growth Factors/metabolism; STAT3 Transcription Factor/metabolism; STAT3 Transcription Factor/genetics; Janus Kinase 2/metabolism; Signal Transduction; Neural Stem Cells/metabolism; Neural Stem Cells/cytology; Neurogenesis/genetics; Neurons/metabolism; Neurons/cytology; Membrane Glycoproteins/metabolism; Membrane Glycoproteins/genetics; Mice, Knockout; Cerebral Cortex; Neural Stem Cells; Neurogenesis; Neurons; Molecular Biology; Developmental Biology

Abstract :

[en] The cell-intrinsic mechanisms underlying the decision of a stem/progenitor cell to either proliferate or differentiate remain incompletely understood. Here, we identify the transmembrane protein Lrig1 as a physiological homeostatic regulator of FGF2-driven proliferation and self-renewal of neural progenitors at early-to-mid embryonic stages of cortical development. We show that Lrig1 is expressed in cortical progenitors (CPs), and its ablation caused expansion and increased proliferation of radial/apical progenitors and of neurogenic transit-amplifying Tbr2+ intermediate progenitors. Notably, our findings identify a previously unreported EGF-independent mechanism through which Lrig1 negatively regulates neural progenitor proliferation by modulating the FGF2-induced IL6/Jak2/Stat3 pathway, a molecular cascade that plays a pivotal role in the generation and maintenance of CPs. Consistently, Lrig1 knockout mice showed a significant increase in the density of pyramidal glutamatergic neurons placed in superficial layers 2 and 3 of the postnatal neocortex. Together, these results support a model in which Lrig1 regulates cortical neurogenesis by influencing the cycling activity of a set of progenitors that are temporally specified to produce upper layer glutamatergic neurons.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

De Vincenti, Ana Paula ; Laboratorio de Neurociencia Molecular y Celular, Instituto de Biología Celular y Neurociencias (IBCN)-CONICET-UBA, Facultad de Medicina. Universidad de Buenos Aires (UBA), Buenos Aires CP1121, Argentina

Bonafina, Antonela ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Laboratorio de Neurociencia Molecular y Celular, Instituto de Biología Celular y Neurociencias (IBCN)-CONICET-UBA, Facultad de Medicina. Universidad de Buenos Aires (UBA), Buenos Aires CP1121, Argentina ; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires, Buenos Aires C1405 BWE, Argentina

Ledda, Fernanda ; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires, Buenos Aires C1405 BWE, Argentina

Paratcha, Gustavo ; Laboratorio de Neurociencia Molecular y Celular, Instituto de Biología Celular y Neurociencias (IBCN)-CONICET-UBA, Facultad de Medicina. Universidad de Buenos Aires (UBA), Buenos Aires CP1121, Argentina

Language :

English

Title :

Lrig1 regulates cell fate specification of glutamatergic neurons via FGF-driven Jak2/Stat3 signaling in cortical progenitors.

Publication date :

01 September 2024

Journal title :

Development

ISSN :

0950-1991

eISSN :

1477-9129

Publisher :

Company of Biologists Ltd, England

Volume :

151

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://journals.biologists.com/dev/article-pdf/doi/10.1242/dev.202879/3563622/dev202879.pdf

Funders :

ANPCyT - Agencia Nacional de Promoción Científica y Tecnológica
CONICET - Consejo Nacional de Investigaciones Científicas y Técnicas

Funding text :

We thank Dr Alejandro Schinder and Ignacio Satorre for technical assistance with the preparation and isolation of retroviral particles; Mar\u0131\u00E1 Mercedes Olivera, Marianela Ceol and Andrea Pecile for animal care; Lic. Nerina Villalba for confocal microscopy assistance; and UBATEC for research grant administration. This work was supported by the Agencia Nacional de Promoci\u00F3n Cient\u0131f\u0301ica y Tecnol\u00F3gica (PICT2019-1472, PICT2019-4597 and PICT2020-1524) and the Consejo Nacional de Investigaciones Cient\u0131f\u0301icas y T\u00E9cnicas (IBCN-P-UE 2018-22920180100009). G.P. and F.L. were supported by an Independent Career Position from the Consejo Nacional de Investigaciones Cient\u0131f\u0301icas y T\u00E9cnicas. A.P.D.V. was supported by fellowships from the Consejo Nacional de Investigaciones Cient\u0131f\u0301icas y T\u00E9cnicas and the Agencia Nacional de Promoci\u00F3n Cient\u0131f\u0301ica y Tecnol\u00F3gica, and A.B. was supported by a fellowship from the Agencia Nacional de Promoci\u00F3n Cient\u0131f\u0301ica y Tecnol\u00F3gica.This work was supported by the Agencia Nacional de Promocio\u0301n Cient\u0131f\u0301 ica y Tecnolo\u0301gica (PICT2019-1472, PICT2019-4597 and PICT2020-1524) and the Consejo Nacional de Investigaciones Cient\u0131f\u0301 icas y Te\u0301cnicas (IBCN-P-UE 2018-22920180100009). G.P. and F.L. were supported by an Independent Career Position from the Consejo Nacional de Investigaciones Cient\u0131f\u0301 icas y Te\u0301cnicas. A.P.D.V. was supported by fellowships from the Consejo Nacional de Investigaciones Cient\u0131f\u0301 icas y Te\u0301cnicas and the Agencia Nacional de Promocio\u0301n Cient\u0131f\u0301 ica y Tecnolo\u0301gica, and A.B. was supported by a fellowship from the Agencia Nacional de Promocio\u0301n Cient\u0131f\u0301 ica y Tecnolo\u0301gica.

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