Ellen Claire Gingrich

All Publications

• Ten3-Lphn2-mediated target selection across the extended hippocampal network demonstrates a repeated strategy for circuit assembly. Current biology : CB Gingrich, E. C., Pederick, D. T., Zhang, Y., Luo, L. 2026

  Abstract

  How do thousands of cell-surface proteins specify billions of neuronal connections in developing brains? We previously found that inverse expression of a ligand-receptor pair, teneurin-3 (Ten3) and latrophilin-2 (Lphn2), in CA1 and subiculum, instructs CA1→subiculum target selection through Ten3-Ten3 homophilic attraction and Ten3-Lphn2 heterophilic reciprocal repulsions. Here, we leveraged conditional knockouts to demonstrate that these mechanisms generalize to several nodes of the extended hippocampal networks, including entorhinal cortex and hypothalamus. Cooperation between attraction and repulsion may differ depending on the order in which developing axons encounter the attractant and repellent subfields. Ten3 and Lphn2 can serve as both ligands for incoming axons and as receptors for their own target selection within the same neuron; Ten3 can be repulsive or attractive as a ligand or receptor. Thus, multifunctionality and repeated use, together with recurrent circuit motifs prevalent in the brain, enable one ligand-receptor pair to instruct target selection of many neurons.

  View details for DOI 10.1016/j.cub.2026.04.038

  View details for PubMedID 42105755

• Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus ELIFE Somaiya, R., Stebbins, K., Gingrich, E. C., Xie, H., Campbell, J. N., Garcia, A. R., Fox, M. A. 2022; 11

  Abstract

  Axons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate Fgf15 and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in Fgf15 expression, as well as in the percentage of interneurons recruited into visual thalamus. Overall, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.

  View details for DOI 10.7554/eLife.79833

  View details for Web of Science ID 000882453000001

  View details for PubMedID 36342840

  View details for PubMedCentralID PMC9640189

• A subpopulation of astrocyte progenitors defined by Sonic hedgehog signaling. Neural development Gingrich, E. C., Case, K., Garcia, A. D. 1800; 17 (1): 2

  Abstract

  BACKGROUND: The molecular signaling pathway, Sonic hedgehog (Shh), is critical for the proper development of the central nervous system. The requirement for Shh signaling in neuronal and oligodendrocyte development in the developing embryo are well established. However, Shh activity is found in discrete subpopulations of astrocytes in the postnatal and adult brain. Whether Shh signaling plays a role in astrocyte development is not well understood.METHODS: Here, we use a genetic inducible fate mapping approach to mark and follow a population of glial progenitor cells expressing the Shh target gene, Gli1, in the neonatal and postnatal brain.RESULTS: In the neonatal brain, Gli1-expressing cells are found in the dorsolateral corner of the subventricular zone (SVZ), a germinal zone harboring astrocyte progenitor cells. Our data show that these cells give rise to half of the cortical astrocyte population, demonstrating their substantial contribution to the cellular composition of the cortex. Further, these data suggest that the cortex harbors astrocytes from different lineages. Gli1 lineage astrocytes are distributed across all cortical layers, positioning them for broad influence over cortical circuits. Finally, we show that Shh activity recurs in mature astrocytes in a lineage-independent manner, suggesting cell-type dependent roles of the pathway in driving astrocyte development and function.CONCLUSION: These data identify a novel role for Shh signaling in cortical astrocyte development and support a growing body of evidence pointing to astrocyte heterogeneity.

  View details for DOI 10.1186/s13064-021-00158-w

  View details for PubMedID 35027088

• Reciprocal repulsions instruct the precise assembly of parallel hippocampal networks. Science (New York, N.Y.) Pederick, D. T., Lui, J. H., Gingrich, E. C., Xu, C., Wagner, M. J., Liu, Y., He, Z., Quake, S. R., Luo, L. 2021; 372 (6546): 1068-1073

  Abstract

  Mammalian medial and lateral hippocampal networks preferentially process spatial- and object-related information, respectively. However, the mechanisms underlying the assembly of such parallel networks during development remain largely unknown. Our study shows that, in mice, complementary expression of cell surface molecules teneurin-3 (Ten3) and latrophilin-2 (Lphn2) in the medial and lateral hippocampal networks, respectively, guides the precise assembly of CA1-to-subiculum connections in both networks. In the medial network, Ten3-expressing (Ten3+) CA1 axons are repelled by target-derived Lphn2, revealing that Lphn2- and Ten3-mediated heterophilic repulsion and Ten3-mediated homophilic attraction cooperate to control precise target selection of CA1 axons. In the lateral network, Lphn2-expressing (Lphn2+) CA1 axons are confined to Lphn2+ targets via repulsion from Ten3+ targets. Our findings demonstrate that assembly of parallel hippocampal networks follows a "Ten3Ten3, Lphn2Lphn2" rule instructed by reciprocal repulsions.

  View details for DOI 10.1126/science.abg1774

  View details for PubMedID 34083484