Biology subjects

Lo Giudice, Q.

Publications and source records attributed to Lo Giudice, Q..

3 recordsLinked to original sources

bioRxiv2024

Developmental emergence of first- and higher-order thalamic neuron molecular identities

The thalamus is organized into nuclei that have distinct input and output connectivities with the cortex. While first-order (FO) nuclei - also called core nuclei - relay input from sensory organs on the body surface and project to primary cortical sensory areas, higher-order (HO) nuclei - matrix nuclei - instead receive their driver input from the cortex and project to secondary and associative areas within cortico-thalamo-cortical loops. Input-dependent processes have been shown to play a critical role in the emergence of FO thalamic neuron identity from a ground state HO neuron identity, yet how this identity emerges during development remains unknown. Here, using single-cell RNA sequencing of the developing embryonic thalamus, we show that FO thalamic identity emerges after HO identity and that peripheral input is critical for the maturation of excitatory, but not inhibitory FO-type neurons. Our findings reveal that subsets of HO neurons are developmentally co-opted into FO-type neurons, providing a mechanistic framework for the diversification of thalamic neuron types during development and evolution. Summary StatementSubsets of higher-order thalamic neurons are developmentally co-opted into first-order type neurons, providing a framework for the diversification of thalamic neuron types during development and evolution.

neuroscience↗

bioRxiv2018

Transcriptional logic of cell fate specification and axon guidance in early born retinal neurons revealed by single-cell mRNA profiling

Retinal ganglion cells (RGC), together with cone photoreceptors, horizontal cells (HC) and amacrine cells (AC), are the first classes of neurons produced in the retina. Here we have profiled 5348 single retinal cells and provided a comprehensive transcriptomic atlas showing the broad diversity of the developing retina at the time when the four early-born cells are being produced. Our results show the transcriptional sequences that establish the hierarchical ordering of early cell fate specification in the retina. RGC maturation follows six waves of gene expression, giving new insight into the regulatory logic of RGC differentiation. Early-generated RGCs transcribe an increasing amount of guidance cues for young peripheral RGC axons that express the matching receptors. Finally, spatial signatures in sub-populations of RGCs allowed to define novel molecular markers that are spatially restricted during the development of the retina. Altogether this study is a valuable resource that identifies new players in mouse retinal development, shedding light on transcription factors sequence and guidance cues dynamics in space and time.

developmental biology↗

bioRxiv2018

Single-cell mRNA profiling reveals heterogeneous combinatorial expression of Hoxd genes during limb development

ABSTRACT (177 words)A global analysis of gene expression during development reveals specific transcription patterns associated with the emergence of various cell types, tissues and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hoxd genes is differentially controlled in space and time in cells that will pattern the digits and the arms. Here we analyze single-cell transcriptomes of limb bud cells and show that Hox genes are expressed in specific combinations that match particular cell types. In the presumptive digits, we find that the expression of Hoxd gene is unbalanced, despite their common genomic proximity to known global enhancers, often expressing only a subset of the five genes transcribed in these cells. We also report that combinatorial expression follows a pseudo-time sequence, suggesting that a progression in combinatorial expression may be associated with cellular diversity in developing digits.\n\nHIGHLIGHTSO_LICollinear expression of Hox genes is only weaved at the tissue scale\nC_LIO_LIEnhancer-sharing to specific target genes is reduced at the single-cell level\nC_LIO_LIHoxd gene combinatorial expression is linked to distinct transcriptional signatures\nC_LIO_LIIn presumptive digits, Hoxd combinations follow a pseudotime trajectory\nC_LI

developmental biology↗