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Published on: June 4, 2014
Pbx1 and Pbx3 cooperatively regulate intermediate progenitor genesis and corticogenesis in the mouse neocortex
Asisa Muchamedin1, Pauline A Ulmke1, Linh Pham1
1Department of Human Genetics, Ruhr University of Bochum, Bochum, Germany.
Frontiers in Cell and Developmental Biology
|July 17, 2026
Summary
Transcription factors Pbx1 and Pbx3 regulate intermediate progenitor cell (IPC) proliferation and differentiation, crucial for neocortical development. Their deletion causes microcephaly and forebrain connectivity defects, highlighting their essential role in brain formation.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Intermediate progenitor cells (IPCs) are critical for generating glutamatergic neurons during neocortical development.
- Transcriptional control of IPC proliferation and differentiation is not fully understood.
Purpose of the Study:
- Identify transcriptional mechanisms regulating IPCs.
- Investigate the role of TALE homeodomain transcription factors Pbx1 and Pbx3 in corticogenesis.
Main Methods:
- Single-nucleus RNA sequencing (snRNA-seq) of Tbr2+ IPCs.
- Bulk RNA sequencing of purified IPCs.
- Conditional dual deletion of Pbx1/Pbx3 using Emx1-Cre.
- CUT&Tag profiling.
Main Results:
- Pbx1 is broadly expressed in IPCs; Pbx3 is enriched in proliferative IPCs.
- Pbx1/Pbx3 deletion reduces IPC proliferation, leading to microcephaly, disrupted cortical lamination, and altered neuron production.
- Mutants exhibit severe forebrain connectivity defects, including agenesis of the anterior commissure and corpus callosum.
- Direct transcriptional targets of Pbx1/Pbx3 include Cux2, Insm1, Lhx2, Myt1l, and Trnp1.
Conclusions:
- Pbx1 and Pbx3 are essential regulators of IPC proliferation and differentiation.
- These factors are critical for proper cortical neuron production and forebrain morphogenesis.
