Browsing by Subject "Notch"

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  • Tervi, Anniina (Helsingin yliopisto, 2020)
    The diversity of different neuronal types lays the foundation for different functions in the brain. The development of different subpopulations and special features of neurons in the central nervous system are still partly unknown. Finding answers to these developmental issues could help in the process of characterisation of cell types and mapping of neuronal networks between the brainstem nuclei in the brain. Previous studies have shown that a ventrolateral neuroepithelial domain in the anterior hindbrain, rV2, produces excitatory (glutamatergic) and inhibitory (GABAergic) neurons, which are related to monoaminergic nuclei in the brainstem (Lahti et al., 2016). In this master’s thesis project, the development of a subpopulation of neurons expressing Gsc2 transcription factor in the interpeduncular nucleus was studied. This project was based on single-cell RNA sequencing results conducted in E13.5 mice. Predicted by single-cell RNA sequencing results, Gsc2 expressing cells are GABAergic interneurons and originate from the rV2 domain of the rhombomere 1 region in the hindbrain. Co-expression pattern with another transcription factor Sall3 with Gsc2 during development was also addressed in the study. Furthermore, the role of Notch signalling in the binary cell fate decision between GABAergic and the glutamatergic fate of rV2 neurons was investigated. Validation of single-cell RNA sequencing results was performed using in situ hybridisation and immunohistochemistry methods with mice embryos at the age of E12.5 and E15.5. This study verified previously shown origin of Gsc2 expressing cells to the rhombomere 1 region and in addition, showed that Gsc2 expressing cells are GABAergic. Co-expression pattern of Gsc2 with Sall3 neither in the rV2 domain nor in the interpeduncular nucleus was seen in our results. In the rV2 domain, the depletion of Notch signalling decreased the expression of differentiating GABAergic neurons. This indicates that Notch has a role in GABAergic neurotransmitter identity during the development of brainstem neurons in mice. Based on our results, Gsc2 could be used as a lineage marker for GABAergic interneurons originating from the rhombomere 1 region and as a marker for a subpopulation of the interpeduncular nucleus. Furthermore, results from the role of Notch signalling could help in discovering the mechanisms related to the determination of neurotransmitter identity in rV2 neurons. Further investigations, in different developmental time points and with additional markers, are needed to verify these results.
  • Ahonen, Maria A.; Haridas, P. A. Nidhina; Mysore, Raghavendra; Wabitsch, Martin; Fischer-Posovszky, Pamela; Olkkonen, Vesa M. (2019)
    MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in pre- and mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling. CDK6 is a validated target of miR-107 and was downregulated upon miR-107 overexpression. Notch3, a signaling receptor involved in adipocyte differentiation, has been shown to decrease upon CDK6 depletion; Here Notch3 and its target Hes1 were downregulated by miR-107 overexpression. In mature adipocytes, miR-107 induces a triglyceride storage defect by impairing glucose uptake and triglyceride synthesis. To conclude, our data suggests that miR-107 has distinct functional roles in preadipocytes and mature adipocytes; Its elevated expression at these different stages of adipocytes may on one hand dampen adipogenesis, and on the other, promote ectopic fatty acid accumulation and reduced glucose tolerance.
  • Sartanen, Juha (Helsingfors universitet, 2016)
    Tässä tutkimuksessa selvitettiin preseniliini 1 ja preseniliini 2 –geenien merkitystä seeprakala-alkioiden kehityksessä ensimmäisten kolmen kehityspäivän ajan. Geenien translaatio estettiin morfolino-oligonukleotidi-injektiolla, jonka jälkeen alkioiden somiittien määrää, sydämen sykettä ja aivojen kokoa seurattiin sekä tutkittiin Notch1a mRNA:n ilmentyminen kunakin päivänä in situ hybridisaatiolla. Tässä työssä ei huomattu eroja ryhmien välillä somiittien määrässä, aivojen koossa eikä sykkeessä varhaiskehitysken aikana. Sen sijaan saatiin viitteitä Notch1a:n ekspression kasvusta preseniliini 1 morfanteilla ja päinvastoin ekspression laskusta preseniliini 2 morfanteilla. Hiirimalleilla ja seeprakaloilla saadut erilaiset tulokset preseniliinien kehityksellisestä merkityksestä antavat viitteitä preseniliini 2:n suuremmasta osuudesta seeprakalojen kehityksessä.