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Francoise Haeseleer

Publications and source records attributed to Francoise Haeseleer.

4 recordsLinked to original sources

A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.

The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in health and disease. We use transcriptomic and epigenomic cortical cell-type taxonomies from mouse and human to define marker genes and putative enhancers and create a large toolkit of transgenic lines and enhancer adeno-associated viruses (AAVs) for selective targeting of cortical cell populations. We report creation and evaluation of fifteen transgenic driver lines, two reporter lines, and >1,000 different enhancer AAV vectors covering most subclasses of cortical cells. The tools reported here have been made publicly available, and along with the scaled process of tool creation, evaluation, and modification, they will enable diverse experimental strategies toward understanding mammalian cortex and brain function.

Animals↗

Calmodulin and Ca2+-binding proteins (CaBPs): variations on a theme.

Ca2+ is a ubiquitous second messenger that frequently exerts its effects through Ca2+-binding proteins. In response to changes in the intracellular [Ca2+], Ca2+-binding proteins modulate the cellular activities of enzymes, channels and structural proteins. Multiple Ca2+-binding proteins are expressed in the retina and, in most cases, in a unique cellular and sub-cellular manner. CaBPs are retinal Ca2+-binding proteins displaying a high similarity to calmodulin (CaM). CaBPs are able to mimic some of the interactions of CaM with effector enzymes, although their physiological role has not yet been resolved. CaBPs could be cell-type specific proteins that play a key role in the Ca2+ signaling of specialized retinal neurons.

Amino Acid Motifs↗

A comparison of immunocytochemical markers to identify bipolar cell types in human and monkey retina.

As more human retinas affected with genetic or immune-based diseases become available for morphological analysis, it is important to identify immunocytochemical markers for specific subtypes of retinal neurons. In this study, we have focused on bipolar cell markers in central retina. We have done single and double labeling using several antisera previously utilized in macaque monkey or human retinal studies and two new antisera (1) to correlate combinations of antisera labeling with morphological types of bipolar cells in human retina, and (2) to compare human labeling patterns with those in monkey retina. Human bipolar cells showed a wide range of labeling patterns with at least ten different bipolar cell types identified from their anatomy and marker content. Many bipolar cell bodies in the outer part of the inner nuclear layer contained combinations of protein kinase C alpha (PKC alpha), Islet-1, glycine, and Go alpha. Bipolar cells labeled with these markers had axons terminating in the inner half of the inner plexiform layer (IPL), consistent with ON bipolar cells. Bipolar cell bodies adjacent to the amacrine cells and with axons in the outer half of the IPL contained combinations of recoverin, glutamate transporter-1, and PKC beta, or CD15 and calbindin. Bipolar cells labeled with these markers were presumed OFF bipolar cells. Calcium-binding protein 5 (CaB5) labeled both putative ON and OFF bipolar cells. Using this cell labeling as a criteria, most cell bodies close to the horizontal cells were ON bipolar cells and almost all bipolar cells adjacent to the amacrine cells were OFF with a band in the middle 2-3 cell bodies thick containing intermixed ON and OFF bipolar cells. Differences were found between human and monkey bipolar cell types labeled by calbindin, CaB5, and CD15. Two new types were identified. One was morphologically similar to the DB3, but labeled for CD15 and CaB5. The other had a calbindin-labeled cell body adjacent to the horizontal cell bodies, but did not contain any accepted ON markers. These results support the use of macaque monkey retina as a model for human, but caution against the assumption that all labeling patterns are identical in the two primates.

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