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

• 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