ePoster

PBX1 AND PBX3 COOPERATIVELY REGULATE INTERMEDIATE PROGENITOR GENESIS AND CORTICOGENESIS IN THE MOUSE NEOCORTEX

Asisa Muchamedinand 9 co-authors

Ruhr University Bochum

FENS Forum 2026 (2026)
Barcelona, Spain
Board PS03-08AM-460

Presentation

Date TBA

Board: PS03-08AM-460

Poster preview

PBX1 AND PBX3 COOPERATIVELY REGULATE INTERMEDIATE PROGENITOR GENESIS AND CORTICOGENESIS IN THE MOUSE NEOCORTEX poster preview

Event Information

Poster Board

PS03-08AM-460

Abstract

Intermediate progenitor cells (IPCs) are essential neuronal precursors that generate the majority of glutamatergic projection neurons during neocortical development. Despite their pivotal role in corticogenesis, the transcriptional programs governing IPC genesis and maintenance remain incompletely understood. By integrating bulk RNA sequencing and single-cell transcriptomic profiling of purified IPCs, we identify the transcription factors Pbx1 and Pbx3 as IPC-enriched regulators. Conditional dual deletion of Pbx1/Pbx3 in the dorsal telencephalon at the onset of neurogenesis (Emx1-Cre) markedly reduced the IPC pool and neuronal output during embryonic stages. At postnatal stages, Pbx1/Pbx3 mutants exhibited microcephaly characterized by reduced cortical size, severe loss of upper-layer neurons, migration defects, and mispositioned neurons. These structural alterations were accompanied by thinning of the corpus callosum, loss of the anterior commissure, and impaired interhemispheric connectivity. Integrated transcriptomic and CUT&Tag analysis further revealed Cux2, Insm1, Lhx2 Myt1l, and Trnp1 as novel Pbx1/Pbx3 targets. Together, our findings identify Pbx1 and Pbx3 as critical transcription factors required for IPC genesis, cortical neuron production, and proper forebrain morphogenesis.

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