Impact of c-JUN deficiency on thalamus development in mice and human neural models DOI Creative Commons
Jiantao Shi, Qing Chen, Jiaming Lai

и другие.

Cell & Bioscience, Год журнала: 2024, Номер 14(1)

Опубликована: Дек. 20, 2024

Abstract Background c-Jun is a key regulator of gene expression. Through the formation homo- or heterodimers, c-JUN binds to DNA and regulates transcription. While plays crucial role in embryonic development, its impact on nervous system development higher mammals, especially for some deep structures, example, thalamus diencephalon, remains unclear. Methods To investigate influence early knockout (KO) mice KO H1 stem cells (ESCs)-derived neural progenitor (NPCs), cerebral organoids (COs), (ThOs) models were used. We detected dysplasia via histological examination immunofluorescence staining, omics analysis, loss/gain function analysis. Results At day 14.5, exhibited sparseness fibers brain ventricular parenchyma malformation diencephalon. The absence accelerated induction NPCs but impaired extension human neuronal cultures. COs lacking displayed robust PAX6 + /NESTIN exterior layer lacked fibers-connected core. Moreover, subcortex-like areas defective characteristics with transcription factor 7 like 2-positive cells. Notably, guided ThOs, led inadequate patterning sparse internal nerve fibers. Chromatin accessibility analysis confirmed less accessible chromatin state genes related thalamus. Overexpression rescued these defects. RNA-seq identified 18 significantly down-regulated including RSPO2, WNT8B, MXRA5, HSPG2 PLAGL1 while 24 MSX1, CYP1B1, LMX1B, NQO1 COL2A1 up-regulated. Conclusion Our findings from vivo vitro experiments indicate that depletion impedes renders susceptible during mouse ThO patterning. work provides evidence first time play important roles thalamus/diencephalon development.

Язык: Английский

Developmental and behavioral phenotypic outcomes associated with Tubulinopathy conditions DOI
Deborah J. Fidler,

Kaylyn Van Deusen,

Thomas D. Cushion

и другие.

International review of research in developmental disabilities, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

0
Impact of c-JUN deficiency on thalamus development in mice and human neural models DOI Creative Commons
Jiantao Shi, Qing Chen, Jiaming Lai

и другие.

Cell & Bioscience, Год журнала: 2024, Номер 14(1)

Опубликована: Дек. 20, 2024

Abstract Background c-Jun is a key regulator of gene expression. Through the formation homo- or heterodimers, c-JUN binds to DNA and regulates transcription. While plays crucial role in embryonic development, its impact on nervous system development higher mammals, especially for some deep structures, example, thalamus diencephalon, remains unclear. Methods To investigate influence early knockout (KO) mice KO H1 stem cells (ESCs)-derived neural progenitor (NPCs), cerebral organoids (COs), (ThOs) models were used. We detected dysplasia via histological examination immunofluorescence staining, omics analysis, loss/gain function analysis. Results At day 14.5, exhibited sparseness fibers brain ventricular parenchyma malformation diencephalon. The absence accelerated induction NPCs but impaired extension human neuronal cultures. COs lacking displayed robust PAX6 + /NESTIN exterior layer lacked fibers-connected core. Moreover, subcortex-like areas defective characteristics with transcription factor 7 like 2-positive cells. Notably, guided ThOs, led inadequate patterning sparse internal nerve fibers. Chromatin accessibility analysis confirmed less accessible chromatin state genes related thalamus. Overexpression rescued these defects. RNA-seq identified 18 significantly down-regulated including RSPO2, WNT8B, MXRA5, HSPG2 PLAGL1 while 24 MSX1, CYP1B1, LMX1B, NQO1 COL2A1 up-regulated. Conclusion Our findings from vivo vitro experiments indicate that depletion impedes renders susceptible during mouse ThO patterning. work provides evidence first time play important roles thalamus/diencephalon development.

Язык: Английский

Процитировано

0