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Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants
Author(s) -
Zhao Yangu,
Flandin Pierre,
Long Jason E.,
Cuesta Melissa Dela,
Westphal Heiner,
Rubenstein John L.R.
Publication year - 2008
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21772
Subject(s) - interneuron , biology , ganglionic eminence , homeobox , transcription factor , parvalbumin , neuroscience , dlx5 , genetics , gene , central nervous system , cerebrum , inhibitory postsynaptic potential
Here we analyze the role of the Lhx6 lim‐homeobox transcription factor in regulating the development of subsets of neocortical, hippocampal, and striatal interneurons. An Lhx6 loss‐of‐function allele, which expresses placental alkaline phosphatase (PLAP), allowed analysis of the development and fate of Lhx6‐expressing interneurons in mice lacking this homeobox transcription factor. There are Lhx6 + ;Dlx + and Lhx6 − ;Dlx + subtypes of tangentially migrating interneurons. Most interneurons in Lhx6 PLAP/PLAP mutants migrate to the cortex, although less efficiently, and exhibit defects in populating the marginal zone and superficial parts of the neocortical plate. By contrast, migration to superficial parts of the hippocampus is not seriously affected. Furthermore, whereas parvalbumin + and somatostatin + interneurons do not differentiate, NPY + interneurons are present; we suggest that these NPY + interneurons are derived from the Lhx6 − ;Dlx + subtype. Striatal interneurons show deficits distinct from pallial interneurons, including a reduction in the NPY + subtype. We provide evidence that Lhx6 mediates these effects through promoting expression of receptors that regulate interneuron migration (ErbB4, CXCR4, and CXCR7), and through promoting the expression of transcription factors either known (Arx) or implicated (bMaf, Cux2, and NPAS1) in controlling interneuron development. J. Comp. Neurol. 510:79–99, 2008. © 2008 Wiley‐Liss, Inc.