A structural profile-based computational screen was used to identify neuropoietin (NP), a new cytokine. The np gene is localized in tandem with the cardiotrophin-1 gene on mouse chromosome 7. NP shares structural and functional features with ciliary neurotrophic factor (CNTF), cardiotrophin-1, and cardiotrophin-like cytokine. It acts through a membrane receptor complex comprising CNTF receptor-␣ component (CNTFR␣), gp130, and leukemia inhibitory factor receptor to activate signal transducer and activator of transcription 3 signaling pathway. NP is highly expressed in embryonic neuroepithelia. Strikingly, CNTFR␣, but not its alternate ligands, CNTF and cardiotrophinlike cytokine, is expressed at the same developmental stages. NP is also observed in retina and to a lesser extent in skeletal muscle. Moreover, NP could sustain the in vitro survival of embryonic motor neurons and could increase the proliferation of neural precursors when associated to epidermal growth factor and fibroblast growth factor 2. Thus, NP is a new ligand for CNTFR␣, with important implications for murine nervous system development.

In the neocortex, neuronal nitric oxide (NO) synthase (nNOS) is essentially expressed in two classes of GABAergic neurons: type I neurons displaying high levels of expression and type II neurons displaying weaker expression. Using immunocytochemistry in mice expressing GFP under the control of the glutamic acid decarboxylase 67k (GAD67) promoter, we studied the distribution of type I and type II neurons in the barrel cortex and their expression of parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP). We found that type I neurons were predominantly located in deeper layers and expressed SOM (91.5%) while type II neurons were concentrated in layer II/III and VI and expressed PV (17.7%), SOM (18.7%), and VIP (10.2%). We then characterized neurons expressing nNOS mRNA (n = 42 cells) ex vivo, using whole-cell recordings coupled to single-cell reverse transcription-PCR and biocytin labeling. Unsupervised cluster analysis of this sample disclosed four classes. One cluster (n = 7) corresponded to large, deep layer neurons, displaying a high expression of SOM (85.7%) and was thus very likely to correspond to type I neurons. The three other clusters were identified as putative type II cells and corresponded to neurogliaform-like interneurons (n = 19), deep layer neurons expressing PV or SOM (n = 9), and neurons expressing VIP (n = 7). Finally, we performed nNOS immunohistochemistry on mouse lines in which GFP labeling revealed the expression of two specific developmental genes (Lhx6 and 5-HT3A). We found that type I neurons expressed Lhx6 but never 5-HT3A, indicating that they originate in the medial ganglionic eminence (MGE). Type II neurons expressed Lhx6 (63%) and 5-HT3A (34.4%) supporting their derivation either from the MGE or from the caudal ganglionic eminence (CGE) and the entopeduncular and dorsal preoptic areas. Together, our results in the barrel cortex of mouse support the view that type I neurons form a specific class of SOM-expressing neurons while type II neurons comprise at least three classes.

Cortical interneurons originate from subpallial precursors and migrate into the cortex during development. Using genetic lineage tracing in transgenic mice we examine the contribution of two germinal zones, the septum and the lateral ganglionic eminence/caudal ganglionic eminence (LGE/CGE) to interneurons of the cortex. We find that the septal neuroepithelium does not generate interneurons for the neocortex. There is, however, clear migration of cells from the LGE/CGE to the cortex. Comparison of the dynamics of cortical colonization by the two major cohorts of interneurons originating in the medial ganglionic eminence (MGE) and the LGE/CGE has shown differences in the timing of migration and initial route of entry into the cortex. LGE/CGE-derived interneurons enter the cortex later than the MGE-derived ones. They invade the cortex through the subventricular/intermediate zone route and only later disperse within the cortical plate and the marginal zone. During the first postnatal week MGE interneurons move extensively to acquire their laminar position within the cortical plate whereas LGE/CGE-derived cells remain largely within the upper layers of the cortex. The two populations intermingle in the adult cortex but have distinct neurochemical properties and different overall distributions. LGE/CGE-derived interneurons account for one third of the total GABAergic interneuron population in the adult cortex.