EPIC: region-free ganglionic eminence (MGE/CGE/LGE) lineage classes for GABAergic neurons #3789

Summary

Ganglionic eminence (GE) lineage gives a general classification for telencephalic GABAergic neurons. CL's GE-lineage classes are currently either restricted to cerebral cortex or interneuron-only. Mouse and primate data both show GE-derived GABAergic types across cortical and subcortical regions:

• the whole mouse brain taxonomy (Yao 2023);
• the HMBA basal ganglia consensus taxonomy (CS20250428), whose classes are explicitly CN LGE GABA, CN MGE GABA and CN CGE GABA.

This epic asks for region-free lineage classes and the fixes needed to hang existing terms under them.

Evidence

Location. Fraction of each WMB subclass's MERFISH cells (Yao 2023) by division:

Provenance. The BG↔WMB correspondences come from a MapMyCells annotation transfer, summarised as a curated crosswalk; they will be re-checked against the raw MapMyCells output. Each BG lineage is the BG taxonomy's class assignment.

Consequence in current CL. The BG-derived primate terms in the striatum are inferred to be cerebral cortex neurons. For example, STR SST-CHODL GABA … (Primate) (CL:4310123), VIP GABA … (Primate) (CL:4310127) and LAMP5-CXCL14 GABA … (Primate) (CL:4310084) are all inferred subclasses of cerebral cortex neuron and cerebral cortex GABAergic interneuron, because their lineage/marker parents carry cortical soma location.

Requested changes

MGE

• New: medial ganglionic eminence derived GABAergic neuron. GABAergic neuron ⊓ develops from some medial ganglionic eminence (UBERON:0004024), with no location. The genus is neuron, not interneuron, so it can cover MGE-derived projection and cholinergic types (e.g. striatal/pallidal cholinergic-GABAergic neurons).
• Re-parent medial ganglionic eminence derived interneuron (CL:4023063) and medial ganglionic eminence derived GABAergic interneuron (CL:4023069, cortex) under it. CL:4023069 stays as the cortical subclass.

CGE

• Logical definition for caudal ganglionic eminence derived neuron (CL:4042039), which currently has none: neuron ⊓ develops from some caudal ganglionic eminence (UBERON:0004026).
• New: caudal ganglionic eminence derived GABAergic neuron, with no location.
• Fix caudal ganglionic eminence derived interneuron (CL:4023064). It is asserted under cerebral cortex GABAergic interneuron, but CGE-derived VIP and LAMP5-CXCL14 types also occur in striatum (BG taxonomy). Either drop the cortical assertion, or rename/redefine it as the cortical subclass and add a region-free parent.

LGE

• New: lateral ganglionic eminence derived GABAergic neuron, under existing lateral ganglionic eminence derived neuron (CL:4023035), which is already region-free. Medium spiny neurons and arkypallidal neurons would classify here.

Relationship to open requests

• Reconcile with caudal ganglionic eminence derived GABAergic neuron of the cerebral nuclei #2752, medial ganglionic eminence derived GABAergic neuron of the cerebral nuclei #2753 and NTR lateral ganglionic eminence derived GABAerigic neuron of the cerebral nuclei #2756, which request CGE-, MGE- and LGE-derived GABAergic neurons of the cerebral nuclei. Those would become region-restricted subclasses of the region-free classes above.

Not included (for discussion)

The BG taxonomy also has non-GE telencephalic/diencephalic GABAergic groupings, e.g. CN LHX8 GABA (prototypic GPe and basal-forebrain LHX6-LHX8-GBX1 types) and F M GATA3 GABA (nigral/VTR GATA3 projection types). Their developmental origin isn't stated, so marker-defined classes may be safer than lineage claims. They are left out of this epic.

Related: #3321 (Basal Ganglion product EPIC), #3566.