scholarly journals A subpopulation of astrocyte progenitors defined by Sonic hedgehog signaling

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Ellen C. Gingrich ◽  
Kendra Case ◽  
A. Denise R. Garcia

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.

2020 ◽  
Author(s):  
Ellen Gingrich ◽  
Kendra Case ◽  
A. Denise R. Garcia

ABSTRACTThe 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. Here, we show that Shh signaling also operates in a subpopulation of progenitor cells that generate cortical astrocytes. In the neonatal brain, cells expressing the Shh target gene, Gli1, are found in the subventricular zone (SVZ), a germinal zone harboring astrocyte progenitor cells. Using a genetic inducible fate mapping strategy, we show that these cells give rise to half of the cortical astrocyte population, suggesting that the cortex harbors astrocytes from different lineages. Shh activity in SVZ progenitor cells is transient but recurs in a subpopulation of mature astrocytes localized in layers IV and V in a manner independent of their lineage. These data identify a novel role for Shh signaling in cortical astrocyte development and support a growing body of evidence pointing to astrocyte heterogeneity.


Author(s):  
Steven A. Hill ◽  
Marissa Fu ◽  
A. Denise R. Garcia

Abstract Astrocytes are complex cells that perform a broad array of essential functions in the healthy and injured nervous system. The recognition that these cells are integral components of various processes, including synapse formation, modulation of synaptic activity, and response to injury, underscores the need to identify the molecular signaling programs orchestrating these diverse functional properties. Emerging studies have identified the Sonic hedgehog (Shh) signaling pathway as an essential regulator of the molecular identity and functional properties of astrocytes. Well established as a powerful regulator of diverse neurodevelopmental processes in the embryonic nervous system, its functional significance in astrocytes is only beginning to be revealed. Notably, Shh signaling is active only in discrete subpopulations of astrocytes distributed throughout the brain, a feature that has potential to yield novel insights into functional specialization of astrocytes. Here, we discuss Shh signaling and emerging data that point to essential roles for this pleiotropic signaling pathway in regulating various functional properties of astrocytes in the healthy and injured brain.


2019 ◽  
Vol 7 ◽  
pp. 3
Author(s):  
Lu Zheng ◽  
Chen Rui ◽  
Hao Zhang ◽  
Jing Chen ◽  
Xiuzhi Jia ◽  
...  

The Sonic hedgehog (SHH) signaling pathway is essential for embryonic development and tissue regeneration. The dysfunction of SHH pathway is involved in a variety of diseases, including cancer, birth defects, and other diseases. Here we reviewed recent studies on main molecules involved in the SHH signaling pathway, specifically focused on their function in epithelial tissue and appendages development, including epidermis, touch dome, hair, sebaceous gland, mammary gland, tooth, nail, gastric epithelium, and intestinal epithelium. The advance in understanding the SHH signaling pathway will give us more clues to the mechanisms of tissue repair and regeneration, as well as the development of new treatment for diseases related to dysregulation of SHH signaling pathway.


2017 ◽  
Vol 436 (1-2) ◽  
pp. 111-117 ◽  
Author(s):  
Celio J. da Costa Fernandes ◽  
Augusto Santana do Nascimento ◽  
Rodrigo A. da Silva ◽  
Willian F. Zambuzzi

Neuron ◽  
2011 ◽  
Vol 71 (2) ◽  
pp. 250-262 ◽  
Author(s):  
Rebecca A. Ihrie ◽  
Jugal K. Shah ◽  
Corey C. Harwell ◽  
Jacob H. Levine ◽  
Cristina D. Guinto ◽  
...  

2016 ◽  
Vol 59 (2) ◽  
pp. 167-172
Author(s):  
Parisa Nadri ◽  
Saeid Ansari-Mahyari ◽  
Azadeh Zahmatkesh

Abstract. Sonic Hedgehog (SHH) is a signaling pathway mediated through a receptor system which seems to have effects on oocyte maturation and embryonic development. Purmorphamine is an SHH agonist that performs a crucial role in the regulation of the activity of SHH receptors and downstream transcription factors. The aim of this study was to analyze the effect of purmorphamine on the mRNA expression of SHH signaling downstream molecules (Patched1, Glioma-Associated Oncogene1, Smoothened, Histone Deacetylase1, Histone Deacetylase2 and Histone Deacetylase3) in ovine two-cell embryo. Ovaries were obtained from a slaughterhouse, and cumulus–oocyte complexes were aspirated and cultured in maturation media containing 0, 250 or 500 ng mL−1 purmorphamine. Then, oocytes were fertilized and cultured in a CR1 culture medium and after 24 h, two-cell embryos were collected for RNA extraction. Gene expression was evaluated by real-time polymerase chain reaction (PCR). Results indicated that in 250 ng mL−1 purmorphamine, Smo, Ptch1 and Hdac3 expression reduced, Hdac1 expression increased, and Gli1 and Hdac2 expression levels did not change. In 500 ng mL−1 purmorphamine, Gli1 and Smo transcripts increased, while Ptch1, Hdac2 and Hdac3 transcripts decreased. Regarding to the presence of SHH signaling molecules in two-cell embryos and their response to purmorphamine, it can be suggested that SHH signaling is probably active before embryonic genome activation in ovine embryos.


2018 ◽  
Vol 19 (10) ◽  
pp. 3040 ◽  
Author(s):  
Amankeldi A. Salybekov ◽  
Ainur K. Salybekova ◽  
Roberto Pola ◽  
Takayuki Asahara

The Hedgehog (HH) signaling pathway plays an important role in embryonic and postnatal vascular development and in maintaining the homeostasis of organs. Under physiological conditions, Sonic Hedgehog (SHH), a secreted protein belonging to the HH family, regulates endothelial cell growth, promotes cell migration and stimulates the formation of new blood vessels. The present review highlights recent advances made in the field of SHH signaling in endothelial progenitor cells (EPCs). The canonical and non-canonical SHH signaling pathways in EPCs and endothelial cells (ECs) related to homeostasis, SHH signal transmission by extracellular vesicles (EVs) or exosomes containing single-strand non-coding miRNAs and impaired SHH signaling in cardiovascular diseases are discussed. As a promising therapeutic tool, the possibility of using the SHH signaling pathway for the activation of EPCs in patients suffering from cardiovascular diseases is further explored.


2020 ◽  
Vol 21 (12) ◽  
pp. 4423
Author(s):  
Sanghoon Lee ◽  
Hyo-Gu Kang ◽  
Pil-Soo Jeong ◽  
Tsevelmaa Nanjidsuren ◽  
Bong-Seok Song ◽  
...  

Brilliant cresyl blue (BCB) staining is used to select developmentally competent cumulus-oocyte complexes (COCs) for in vitro maturation (IVM). However, limited attention has been paid to what drives the higher developmental competence of BCB+ COCs. Sonic hedgehog signaling (SHH) is an important signaling pathway for ovarian follicular development and oocyte maturation. Therefore, this study investigated the effect of oocyte quality assessed by BCB staining on cumulus cell expansion, oocyte nuclear maturation, subsequent embryo development, apoptosis levels, and SHH signaling protein expression, in porcine COCs. After IVM, BCB+ COCs exhibited a significantly higher proportion of complete cumulus cell expansion and metaphase II rate in oocytes than BCB- COCs. After in vitro fertilization, the BCB+ group showed a significantly higher monospermy rate, fertilization efficiency, percentage of cleavage and blastocyst formation, with a higher total cell number and a lower apoptosis in blastocysts as compared with the BCB- group. Furthermore, significantly lower apoptosis levels and a higher expression of SHH-signaling proteins in COCs were observed, before and after IVM. In conclusion, high-quality oocytes had a greater potential to expand their surrounding cumulus cells with active SHH signaling and a lower apoptosis. This could provide COCs with a proper environment for maturation, thereby leading to a better subsequent embryo development.


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