FOXG1 sequentially orchestrates subtype specification of postmitotic cortical projection neurons.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35613274.
- Also identified by DOI 10.1126/sciadv.abh3568 and PMC identifier 9132448.
- Licence recorded as CC BY-NC.
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Abstract
The mammalian neocortex is a highly organized six-layered structure with four major cortical neuron subtypes: corticothalamic projection neurons (CThPNs), subcerebral projection neurons (SCPNs), deep callosal projection neurons (CPNs), and superficial CPNs. Here, careful examination of multiple conditional knockout model mouse lines showed that the transcription factor FOXG1 functions as a master regulator of postmitotic cortical neuron specification and found that mice lacking functional FOXG1 exhibited projection deficits. Before embryonic day 14.5 (E14.5), FOXG1 enforces deep CPN identity in postmitotic neurons by activating <i>Satb2</i> but repressing <i>Bcl11b</i> and <i>Tbr1</i>. After E14.5, FOXG1 exerts specification functions in distinct layers via differential regulation of <i>Bcl11b</i> and <i>Tbr1</i>, including specification of superficial versus deep CPNs and enforcement of CThPN identity. FOXG1 controls CThPN versus SCPN fate by fine-tuning <i>Fezf2</i> levels through diverse interactions with multiple SOX family proteins. Thus, our study supports a developmental model to explain the postmitotic specification of four cortical projection neuron subtypes and sheds light on neuropathogenesis.